Oxidative stress plays an important role in the complications of diabetes. This study was designed to investigate the effects of vanadyl sulfate (VS) on the oxidant-antioxidant systems in streptozotocin (STZ)-nicotinamide-induced type 2 diabetes. Wistar rats were administered intraperitoneally 230 mg/kg of nicotinamide 15 min before an intraperitoneal injection of 65 mg/kg STZ. VS was administered in drinking water 0.75 mg¨Mml during 5 weeks. Thirty two male Wistar rats were randomly divided into four groups; control (C), control+VS (C+VS), diabet (D), diabet+VS (D+VS). VS reduced plasma glucose, total cholesterol and triglyceride and tissue malondialdehyde (MDA) levels and increased serum paraoxonase activity in the D+VS group. Plasma MDA level was significantly increased in the C+VS, D and D+VS groups. Glutathione peroxidase activity was significantly higher in the C+VS and D+VS groups. The results of the present study suggest that, related to its antihyperglycemic and antihyperlipidemic effects, VS may be used as a supportive therapeutic agent in diabetes; however, its effects on the oxidant-antioxidant balance should be taken into account.