OBJECTIVE: To provide information about the effects of zofenopril on volvulus using an ischemia-reperfusion model with histochemical and biochemical methods. STUDY DESIGN: Experimental animals were divided into 5 groups, under anesthesia. (1) The sham group (n=7) received only laparotomy, and a 5 cm segment of small intestine was removed approximately 2 cm from the proximal part of the cecum. (2) The second group (n=7) received laparotomy, and the intestine segment was removed for examination. (3) The third group (n= 7) underwent 2 hours of ischemia followed by 2 hours of reperfusion (2 hours of superior mesenteric artery occlusion followed by 2 hours of reperfusion). (4) The fourth group (n=7) received orally 15 mg/kg zofenopril (before laparotomy) after 2 hours of ischemia. Then reperfusion was performed for 2 hours. (5) The fifth group (n=7) received orally 15 mg/kg zofenopril without ischemia. Intestinal tissues were taken, fixed, and embedded in paraffin blocks for histopathological examinations. Blood samples were collected for biochemical analysis. Total antioxidant status, total oxidative status (TOS), and oxidative stress index (OSI) were measured in jejunum tissue. Also, jejunum tissue histopathology was evaluated under a light microscope. RESULTS: Serum TOS levels were significantly different between all groups (p=0.759). OSI levels were significantly different between all groups (p=0.180). Histopathologically, ischemia reperfusion caused microscopic intestinal damage such as mucosal destruction, villus loss, and epithelial cell apoptosis, congestion, and infiltration of inflammatory cells. Oral administration of zofenopril following ischemia resulted in a marked inhibition of apoptosis induction in the stroma and villi epithelium. CONCLUSION: Zofenopril improved the intestinal mucosal damage by relieving oxidative stress and apoptosis after intestinal ischemia-reperfusion. © Science Printers and Publishers, Inc.