The protective effect of black cumin (Nigella sativa = NS) on cadmium-induced oxidative stress was studied in rats. The rats were randomly divided into three experimental groups: A (conrol), B (Cd treated), and C (Cd + NS treated), each containing 10 animals. The Cd-treated and Cd + NS-treated groups were injected subcutaneously daily with CdCl2 dissolved in isotonic NaCl in the amount of 2 mL/kg for 30 d, resulting in a dosage of 0.49 mg Cd/kg/d. The control group was injected with only isotonic NaCl (2 mL/kg/d) throughout the experiment (for 30 d). Three days prior to induction of CdCl2, the Cd + NS-treated group received a daily intraperitoneal injection of 0.2 mL/kg NS until the end of the study. Cd treatment increased significantly the malondialclehyde levels in plasma and erythrocyte (p < 0.01 and p < 0.05, respectively) and also increased significantly the antioxidant levels (superoxide dismutase, glutathione peroxidase, and catalase) (p < 0.05) compared to the control group. Cd + NS treatment decreased significantly the elevated malondialdehyde levels in plasma and erythrocyte (p < 0.01 and p < 0.05, respectively) and also reduced significantly the enhanced antioxidant levels (p < 0.05). Cd treatment increased significantly the activity of iron levels (p < 0.05) in the plasma compared to the control group. Cd + NS treatment decreased the activity of iron levels (p < 0.05) in the plasma compared to the Cd-treated group. In the control group with no treatment, histology of erythrocytes was normal. In the Cd-treated group, there were remarkable membrane destruction and hemolytic changes in erythrocytes. In the Cd + NS-treated group, these changes were less than in the Cd-treated group. Our results show that N. sativa exerts a protective effect against cadmium toxicity.