To evaluate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant markers in streptozotocin (STZ)-induced diabetic rats. Thirty-six male rats were divided into the following four groups: control, GSE-supplemented control, diabetic, and GSE-supplemented diabetic. Beginning on day 7 after STZ injection, the rats were administered GSE (100 mg kg(-1) day(-1) in drinking water for 6 weeks. At the end of week 6, rats were sacrificed by cardiac puncture. Plasma nitric oxide (NO) levels and xanthine oxidase (XO), adenosine deaminase (ADA), and glutathione peroxidase (GPx) activities were analyzed. Both XO and ADA activities increased and NO levels decreased in diabetic rats (P < 0.05). GSE supplementation normalized all of these changes. Antioxidant enzyme activities decreased in diabetic rats compared to the controls (P < 0.05). GSE supplementation increased antioxidant enzyme activities in both diabetic and healthy rats (P < 0.05). These findings suggest that 6 weeks of oral GSE supplementation may prevent oxidative stress and improve antioxidant status in diabetic rats.