Although it has been demonstrated that lazaroids can protect various organs from ischemia reperfusion injury, results obtained in the small intestine have been conflicting. On the other hand, it is not known whether inhibition of lipid peroxidation prevents intestinal ishemia-reperfusion injury. We investigated whether the administration of the aminolazaroid U-74389G had a beneficial effect on the repair process of the intestinal mucosa after transient mesenteric ischemia in a randomized-blind trial. Six groups of rats were subjected to a model of 60 min of intestinal ischemia that was produced by occluding the superior mesenteric artery. At the end of ischemia, U-74389G was administered intravenously and the clamp was removed to allow reperfusion. At 60 min after reperfusion animals were sacrificed and a 10-cm section of terminal ileum was resected. Its efficacy was evaluated by histopathological assessment, measurement of polymorphonuclear leukocytes and the extent of lipid peroxidation by measuring the small intestine tissue malondialdehyde. After 1 h of reperfusion, mucosal damage in both U-74389G-treated rats and control group rats was similar. However, the number of polymorphonuclear leukocytes in the intestinal mucosa was lower in the U-74389G group. Of particular interest was that U-74389G resulted in a statistically significant reduction in the concentration of small intestine tissue malondialdehyde, compared to the controls. When administered in an imitated clinical setting, U-74389G did not prevent intestinal ischemia reperfusion injury, however it protected the rat small intestine from oxidative damage by inhibiting lipid peroxidation.