It is well documented that oxidative stress is a basic mechanism behind the development of diabetic retinopathy (DR). The current study was undertaken to elucidate the possible role of zinc as an antioxidant and a biological membrane stabilizer in the protection against (DR). Male Wistar rats weighing 250 +/- 50 g were made diabetic by injection with a single ip dose of alloxan (100 mg/kg). Another group of rats was simultaneously treated with alloxan (100 mg/kg) and a single ip dose of zinc chloride (ZnCl2) (5 mg/kg). Blood and tissue samples were collected at 24, 48, and 72 h post-treatment in both groups. Diabetic state was confirmed by the determination of plasma glucose levels (significantly elevated at any time of the experiment when compared with controls receiving vehicle). Plasma insulin was significantly increased 24 h after treatment in both alloxan and alloxan plus ZnCl2-treated groups, and then decreased markedly 48 and 72 h post treatment in both groups. Alloxan treatment depleted both retinal and liver glutathione contents. The decrease in retinal and liver GSH in alloxan-treated rats was accompanied with a sustained increase in their thiobarbituric acid (TBA) content. Simultaneous treatment of rats with alloxan and ZnCl2 blunted the sustained increment in plasma glucose induced by alloxan. The combined administration of alloxan and zinc reversed the depleting effect on retinal and hepatic GSH in alloxan-treated rats and reduced the elevations in TBA content of both retinas and livers. At variance with many other antioxidants the current results clearly indicate the beneficial effects of Zn in both controlling hyperglycemia and the protection of the retina against oxidative stress in diabetes which may help set a new direction toward the development of effective treatments of DR.