AIM: The aim of the study was to examine the influence of fats and sugar rich diet on the expression of antioxidative genes in microcirculation of Sprague Dawley (SD) rats of both sexes. MATERIALS AND METHODS: Healthy Sprague-Dawley rats of both sexes, aged 10 months were divided into four groups: control group, group HSHFD, HSHFD + Metformin + HSHFD group and liraglutide group and dietary protocols have been introduced in the period of 4 months. Out of blood vessels of the brain was measured gene expression of antioxidant enzymes (Cu / Zn SOD, MnSOD, EC-SOD, GPx1, catalase and 4) the method of PCR in real time. RESULTS: The treatment caused liraglutidinom lower blood glucose levels in rats whereas in male rats was determined change in blood glucose concentrations. The blood vessels of the brain in rats the expression of genes of MnSOD, EC-SOD and GPxl in all HSHFD groups, the treatment or no treatment, was significantly reduced as compared to the female control group Also, expression GPx1 increased compared to female HSHFD group without treatment. GPx4 expression in blood vessels of the brain in rats decreased significantly in the group with metformin therapy compared to the control group, while increased expression liraglutide GPx4 enzyme measured in the control group. EC-SOD and GPx4 in male blood vessels of the brain were significantly reduced in all groups compared to the control group and the expression of the Cu / Zn SOD in HFHSD group compared to the other groups (p <0.05). Liraglutide increased expression of MnSOD in uspordbi groups with the metformin in the blood vessels of the rat brain. CONCLUSION: The blood glucose level remained within the physiological range using feed enriched with fats and carbohydrates using antidiabetic agents and without administration. Also, diet protocol leads to significant decreases in levels of antioxidant enzima.Primjena antidiabetic agents did not show a significant effect on the expression of the majority of antioxidant enzymes in the brain vessels