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Lead acetate (PbAC) toxicity can occur by either ingestion or inhalation from contaminated surfaces or from the environment. Nigella sativa is a natural product with immense pharmacological properties, which include antioxidant, antibacterial, and antianemia properties. It has been showed to counter the effect of PbAC-induced hematological and biochemical changes in short-term studies. This study hypothesized that the N. sativa (NS) administration will ameliorate the deleterious effects of chronic PbAC toxicity in rats. A total of 75 Sprague Dawley rats were divided into three groups of 25 rats, and each group was further sub-divided into five groups of five rats each. Group 1 rats (negative control) were given distilled water, group 2 (positive control; PC) were given 10 mg/kg of lead acetate (PbAC) daily, and groups 3 (T1), 4 (T2), and 5 (T3) were each given 10 mg/kg of PbAC followed by graded concentrations of powdered seeds of NS; 100, 150, and 200 mg/kg, respectively. Five rats in each group were euthanized at 30, 60, and 90 days for collection of whole blood and selected organs. Whole blood was collected after euthanized via cardio puncture and used to evaluate the complete blood profile, while plasma was used for biochemical analysis. Tissue samples of the liver and kidney were fixed with 10% buffered formalin, processed, and stained with H&E and periodic acid–Schiff (PAS) for the liver. Aggression and fear were increased in the PbAC-exposed group and absent in the T3 group. There was a lower (p