BACKGROUND Alterations in catalase (CAT) and superoxide dismutase (SOD) activity have been reported in diabetes mellitus. Glibenclamide (glyburide), a member of the second-generation sulphonylureas, provides effective treatment for patients with moderate diabetes. The action of the liver plays an important role in its glucose-lowering effect, suggesting that glibenclamide also exerts a direct effect on liver enzyme activities. OBJECTIVE To evaluate the effect of glibenclamide on the activities of antioxidant enzymes (CAT and SOD) in liver and kidney tissue of diabetic rats. METHODS Thirty-nine rats were included in this study. Moderate diabetes mellitus was induced with streptozocin (freshly dissolved in citrate buffer, ph 4.5) 55 mg/kg in 22 rats. Eight of these diabetic rats were left untreated, insulin was administered to six diabetic rats, and glibenclamide was administered to eight rats with moderate diabetes. Liver and kidney CAT and SOD activities were measured in all rats. RESULTS Hepatic CAT and SOD activities were significantly reduced in diabetic animals (p < 0.05 for both activities). Glibenclamide treatment of diabetic rats for 5 weeks reversed the changes observed in diabetic liver tissues (p < 0.05). However, renal CAT and SOD activities were unchanged. In addition, high blood glucose levels of diabetic rats were decreased following glibenclamide treatment. CONCLUSIONS Administration of glibenclamide to diabetic rats reversed diabetes-induced changes, suggesting that glibenclamide may directly increase liver CAT and SOD activity.