The effect of chronic daidzein, a soybean isoflavone, on aortic reactivity of streptozotocin-diabetic rats was studied. Male diabetic rats received daidzein for 7 weeks a week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to PE was significantly lower in daidzein-treated diabetic rats relative to untreated diabetic rats, and endothelium removal abolished this difference. Endothelium-dependent relaxation to ACh was significantly higher in daidzein-treated diabetic rats as compared with diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester and/or indomethacin attenuated it. Two-month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity, and daidzein treatment significantly reversed the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with daidzein could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and prostaglandin-related pathways, and via attenuation of oxidative stress in aortic tissue and endothelium integrity seems essential for this effect. Copyright © 2012 John Wiley & Sons, Ltd.