Objectives: A member of the second-generation sulfonylureas, glyburide (GLY; glibenclamide) provides an effective therapy for patients with type 2 diabetes. It stimulates pancreatic insulin secretion, suggesting that it is effective in the treatment of type 2 diabetes primarily by elevating the circulating insulin levels. However, experimental evidences have indicated that sulfonylureas have also had an extrapancreatic effect, which may directly contribute toward maintaining blood glucose homeostasis during diabetes. Methods: In this study, we administrated GLY to streptozotocin-induced diabetic rats and determined the effects of such treatment on activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) from brain tissue. Results and Discussion: Brain CAT and GPx activities were not significantly different in the diabetic group compared to controls (P>.05), but the SOD activity was significantly reduced in the diabetic group compared to controls (P<.001). GLY treatment of 4 weeks had restored the SOD and CAT enzyme activities in diabetic rat brain (P<.05). In addition, high blood glucose levels of untreated diabetic rats were decreased following the GLY treatment (P<.01). Administration of GLY to diabetic rats restored the diabetes-induced changes, suggesting that GLY could restore the brain SOD and CAT activities. (C) 2009 Elsevier Inc. All rights reserved.