In this study, some underlying mechanisms responsible for the beneficial effect of chronic oral administration of resveratrol on aortic reactivity of streptozotocin (STZ)-diabetic rats were investigated. Male diabetic rats received resveratrol (10 mg/kg/day) for 8 weeks, 1 week after diabetes induction. Treatment of diabetic rats with resveratrol produced a hypoglycaemic effect and there were appropriate changes regarding serum lipids. Resveratrol also attenuated the increased malondialdehyde (MDA) content and reduced activity of superoxide dismutase (SOD) in liver and aortic tissues. Maximum contractile response of endothelium-intact aortic rings to KCl and phenylephrine (PE) was significantly lower in resveratrol-treated diabetic rats relative to untreated diabetics. Endothelium removal abolished the significant difference between resveratrol-treated and untreated diabetic groups regarding contractile response to KCl and PE. Meanwhile, endothelium-dependent relaxation to acetylcholine (ACh) was significantly higher in resveratrol-treated diabetic rats as compared to diabetic group and pretreatment with N(omega)-L-arginine methyl ester (L-NAME) and indomethacin (INDO) significantly attenuated these responses. Chronic treatment with resveratrol may prevent diabetes-related changes in vascular reactivity observed in diabetic rats directly and/or indirectly due to its hypoglycaemic and hypolipidaemic effects and attenuation of lipid peroxidation and through endothelial-derived factors.