Vanadyl sulfate (VS) may reduce oxidative stress related to its hypoglycemic and hypolipidemic effects in diabetes mellitus; besides, as a catalytic element, it may induce lipid peroxidation. Studies investigating effects of VS on the oxidative-antioxidative systems in diabetes yielded conflicting results, and this study was designed to investigate the effects of VS on the oxidative-antioxidative systems in streptozotocin-induced (65 mg/kg) diabetic rats. Vanadyl sulfate was administered in drinking water 0.75 mg/mL during 5 weeks after the induction of diabetes. Thirty-two male Wistar rats were randomly divided into four groups: control (C), control + vanadyl sulfate (C + VS), diabetes (D), and diabetes + vanadyl sulfate (D + VS). Vanadyl sulfate reduced the enhanced glucose, lipid, and tissue malondialdehyde levels and increased the reduced serum paraoxonase and arylesterase activity in the D + VS group. Plasma malondialdehyde level was significantly increased in the C + VS group, compared with the control group. Erythrocyte glutathione peroxidase activity was significantly higher in the C + VS and D + VS groups, compared with the C and the D groups, respectively.The results of the present study suggest that (i) VS has antioxidative potential in streptozotocin-treated rats, and it might be used as a supportive therapeutic agent in uncontrolled diabetes; (ii) VS treatment might play a role in the improvement of serum paraoxonase activity and, thus, inhibit the progression of atherosclerosis; (iii) the prooxidant potential of the VS should be taken into account. (c) 2006 Elsevier Inc. All rights reserved.