Oxidative stress is produced under diabetic conditions and is likely involved in the progression of pancreatic damage found in diabetes. This study was undertaken to evaluate the protective effect of Aegle marmelos leaf extract, a medicinal plant, on the tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Ethanol extract of A. marmelos was administered orally for 30 days (150 mg/kg body weight/day) to diabetic rats. Activity of the three primary scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), levels of glutathione, and lipid peroxidation were estimated in plasma and pancreas of diabetic rats and compared to the reference drug, glibenclamide (600 microg/kg body weight/day). A significant increase in the levels of plasma glucose, vitamin E, ceruloplasmin, lipid peroxides, and a concomitant decrease in the levels of vitamin C and reduced glutathione were observed in diabetic rats. The activities of antioxidant enzymes were altered in diabetic rats. These alterations were reverted back to near normal levels after treatment with A. marmelos and glibenclamide. Histopathological studies also revealed the protective effect of A. marmelos on pancreatic beta-cells. The present study indicates that extract of A. marmelos modulates the activity of enzymic and nonenzymic antioxidants and enhances the defense against reactive oxygen species-generated damage in diabetic rats.