The aim of the present study was to evaluate the possible protective effects of Nigella sativa L. (NS) against -cell damage from streptozotocin (STZ)-induced diabetes in rats. STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce diabetes. NS (0.2 ml/kg/day, i.p.) was injected for 3 days prior to STZ administration, and these injections were continued throughout the 4-week study. Oxidative stress is believed to play a role in the pathogenesis of diabetes mellitus (DM). To assess changes in the cellular antioxidant defense system, we measured the activities of antioxidant enzymes (such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT)) in pancreatic homogenates. We also measured serum nitric oxide (NO) and erythrocyte and pancreatic tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, to determine whether there is an imbalance between oxidant and antioxidant status. Pancreatic -cells were examined by immunohistochemical methods. STZ induced a significant increase in lipid peroxidation and serum NO concentrations, and decreased antioxidant enzyme activity. NS treatment has been shown to provide a protective effect by decreasing lipid peroxidation and serum NO, and increasing antioxidant enzyme activity. Islet cell degeneration and weak insulin immunohistochemical staining was observed in rats with STZ-induced diabetes. Increased intensity of staining for insulin, and preservation of -cell numbers were apparent in the NS-treated diabetic rats. These findings suggest that NS treatment exerts a therapeutic protective effect in diabetes by decreasing oxidative stress and preserving pancreatic -cell integrity. Consequently, NS may be clinically useful for protecting -cells against oxidative stress. Key words: Nigella sativa L.; diabetes mellitus; streptozotocin; oxidative stress Diabetes mellitus (DM) results in severe metabolic imbalances and pathological changes in many tissues. Oxidative stress plays an important role in the etiology of diabetes and diabetic complications (Baynes and Thorpe, 1996). Diabetics and experimental animal models exhibit high oxidative stress due to persistent and chronic hyperglycemia, which depletes the activity of the antioxidative defense system and thus promotes the generation of free radicals (Baynes, 1991). These animal models include alloxan-or streptozotocin (STZ)-induced diabetic rats and mice (Gillery et al., 1989).STZ, an antibiotic produced by Streptomyces achromogenes, is the most commonly used agent in experimental diabetes (Rakieten et al., 1963). The mechanism by which STZ destroys -cells of the pancreas and induces hyperglycemia is still unclear. Many actions have been attributed to STZ that are similar to what has been described for the diabetogenic action of alloxan, including damage to the pancreatic -cell membrane (Bhattacharya, 1954) and depletion of intracellular nicotineamid adenine dinucleotide in islet cells (Schein et al., 1973). In addition, STZ has been shown to induce DNA strand...