Infarction of the spleen is a rare condition accompanied by serious comorbidity. In literature protective and therapeutic effect of pentadecapaptid BPC 157 is well documented in many pathological conditions including ischemia induced states. It is suggested that the model of action of BPC 157 through the NO system. Aim: The aim was to explore the therapeutic effect of BPC 157 on ischemic lesion of rat spleen in early and late phase of their development and monitoring evolution of the lesion in reperfusion. The effect of BPC 157 was compared with the effect of L-NAME and L-arginine on equal tissue and in the same circumstances. Material and methods: The material was Wistar rat females weight 200-300g and the trials were carried out with the circulation cut off in the spleen in a way that in each trial a group was given BPC 157 (10 µg, 10ng/kg i.p.), and the second group was control. After that followed a macroscopic and microscopic analysis of results. Results: The macroscopic measurements represented the value of the spleen’s infracted area (30 minutes of ischemia) and microscopic preparation (12, 18 and 24 hours of ischemia) took measurements of healthy area per 10 visual microscopic fields. In all trials p<0,005. BPC 157 given in both doses significantly decreased the infracted area and enlarged the percentage of healthy spleen area in rats whose spleen’s blood vessels were ligated. Conclusion: BPC 157 has an effect on ischemic lesion in rat spleena, as prevention of leasion development and as therapy of an advanced lesion; L-NAME and L-arginine changes the evolution of the ischemic lesion of the spleen; and BPC 157 has a therapeutic effect in conditions of NO synthase blockade (L-NAME) and application NO precursor (L-arginine).