Introduction. Inflammatory bowel diseases represent a group of chronic autoimmune diseases of the gastrointestinal tract which exact etiopathogenesis is unknown. Previous studies suggested an association between dipeptidyl peptidase IV (DPP IV/CD26) and molecular mechanisms involved in the process of intestinal inflammation. It has been shown that this molecule plays an important role in the breakdown of neuroimmunoendocrine mediators involved in maintaining the integrity of intestinal mucosa and the occurrence of inflammatory events. Objectives. This research is based on the hypothesis that DPP IV/CD26 possesses an important neuroimmunomodulative role, given that the biological activity of many neuropeptides and interleukins is directly influenced by this molecule. The aim of this study was to investigate the causative connections between DPP IV/CD26 and Crohn's disease, by monitoring the profile of mediators involved in the neuroimmune responses during emergence and course of chemically induced colitis in CD26 deficient and wild type mice. Materials and methods. The model of Crohn's disease in mice was induced by rectal, intraluminal application of trinitrobenzensulfonic acid (TNBS) ethanol solution. In order to examine the in vivo properties of DPP IV/CD26 in the development and healing of inflammation, colitis was induced in CD26 deficient (CD26-/-) and wild type mouse strain C57BL/6, of same gender and age. The control group was represented by the appropriate animal strain which has been rectally applied, under same conditions, sterile physiological solution or ethanol solution. Colitis development, intensity and healing were followed at different time intervals based on clinical and histological parameters at the systemic and local levels in both strains of experimental animals. The degree of colonic mucosa damage was assessed by evaluation of macroscopic changes, histopathological analysis, microscopic indices of damage, and histomorphometric analysis of paraffin tissue sections at different time intervals during the development and healing of inflammatory changes. DPP IV/CD26 activity in C57BL/6 mouse strain and the activity of DPP IV/CD26-like enzymes in CD26 deficient animals in serum, brain and large intestine were determined spectrophotometrically. Protein expression of DPP IV/CD26 in brain and colon of C57BL/6 mice was determined by Western blot technique. Systemic (serum) and local (in brain and colon protein extracts) concentrations of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were determined by specific immunoenzymatic tests (ELISA), and their protein expressions by Western blot technique. Concentrations of the proinflammatoty interleukin 6 (IL-6) and antiinflammatory interleukin 10 (IL-10) in circulation and in brain and colon tissue extracts were also determined by specific immunoenzymatic tests (ELISA). Results. The development of chemically induced colitis in C57BL/6 and CD26 deficient mice leads to clinical manifestations of the disease, statistically significant changes in body weight, liver and spleen weights, macroscopic and histological changes in the colon, which confirms the establishment of a model of colitis. During the development and healing of colitis, CD26 molecule deficiency resulted in histological changes in the manifestation of inflammatory process: in CD26 deficient animals inflammatory changes were mainly localized, with transmural inflammatory changes, while in C57BL/6 animals a diffuse inflammation that affects the whole intestinal circumference could be found. Targeted immunochemical parameters (enzyme activities, concentrations of neuropeptides, interleukins concentrations) resulted in statistically significant changes at the systemic and local levels in both strains of experimental animals, in mice with induced colitis compared to controls, but also between mice strains. DPP IV activity in C57BL/6 animals was statistically significantly decreased in serum, brain and colon in animals with induced colitis, compared to the control group. In the acute phase of colitis, in CD26-/- animals, statistically significant differences in changes in concentrations of NPY and VIP and IL-6 and IL-10 in circulation and at the local level (in brain and colon) were found, compared to C57BL/6 animals. Concentrations of anti-inflammatory mediators IL-10 and VIP were statistically significantly higher in serum and at local levels in CD26-/- animals, while C57BL/6 animals had higher concentrations of NPY in brain and colon. Conclusion. The TNBS-colitis (Crohn-like colitis) has been established in both mouse strains, as confirmed by statistically significant changes in clinical and histological parameters at local and systemic level, with corresponding differences in histological inflammatory changes. During the development and healing of colitis in CD26-/- animals, significant changes in systemic and tissue concentrations of NPY, VIP, IL-6 and IL-10 occurred, compared to C57BL/6 animals. The results obtained in this study indicate that inflammatory changes in immunobiochemical parameters at the level of the colon reflect in changes of those parameters in the brain. The results of this study indicate that DPP IV/CD26 possesses also neuroimmunomodulative properties during development and healing of inflammatory bowel disease in mice.