Purpose: Prolonged surgical procedures and some clinical conditions such as surgeries of thoracoabdominal aorta, mesenteric ischemia, cardiopulmonary bypass, strangulated hernias and neonatal necrotizing enterocolitis may cause decreased perfusion and injury of relevant organs and tissues. After reperfusion, injuries may get worse, leading to ischemia-reperfusion (I/R) injury. Reperfusion following arterial clamping allows oxygen to ischemic tissues and produce injury by multiple mechanisms, including neutrophilic infiltration, intracellular adhesion molecules, and generation of reactive oxygen radicals. In this study with the analysis of SOD, MDA and Caspase-3 levels, we aimed to investigate the effect of topiramate on the outcome of I/R occured after abdominal aorta clamping on rats. Materials and Methods: Totaly 24 Sprague-Dawley male rats were randomly divided into three experimental groups; the control group (n = 8), I/R (n = 8) and I/R+ topiramate (n = 8). Topiramate (100 mg/kg/day); 50 mg/kg (single dose) was administered intraperitoneally after being diluted with saline 5 days before I/R. Results: The intestinal tissue of the ischemia group displayed hemorrhage, Crypts of Lieberkuhn degeneration, ulceration, vascular congestion and edematous fields as a result of aortic occlusion. We also observed that MDA levels and Caspase-3 positivity increased and SOD levels decreased in the small intestine. However, topiramate administration decreased Crypts of Lieberkuhn degeneration, ulceration, vascular congestion and edematous fields, Caspase-3 positivity, and MDA levels. Conclusion: Our findings suggest that topiramate is effective against aortic occlusion-induced intestinal injury by reducing oxidative stress and apoptosis.