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Aim: This study was designed to evaluate the prophylactic effect of Nigella sativa (NS) treatment on toxic effects induced by lead acetate (LA) on the reproductive hormones, spermiogram and gonadal histology of rats. Materials and Methods: A total of 20 Sprague-Dawley rats were divided into four groups of five rats each. Group 1 (negative control [NC]) was the NC and was given distilled water, Group 2 served as the positive control (PC) and was administered 10 mg/kg/day of LA per overall survival (OS), Group 3 (T1) was administered 200 mg/kg/daily of NS per OS for a month, and Group 4 (T2) was pretreated with 200 mg/kg/daily of NS per OS for 1 month, followed by 10 mg/kg/daily of LA alone per OS for another. The rats were euthanized at the end of the experimental period for collection of blood and the right caudal epididymis and testis. Serum was used for determination of reproductive hormones by using radioimmunoassay kits. The epididymal segment was cut and homogenized in phosphate-buffered saline, and the homogenate was used for determination of the spermiogram parameters such as sperm concentration, sperm viability, percentage of live sperm, motility and abnormality. Both the epididymis and testis were fixed in 10% buffered formalin for histological processing. Results: The sperm concentration, general, and individual motilities were higher (p0.05) between control and T2. The concentration of follicle-stimulating hormone (FSH) was comparable (p>0.05) in all groups, while testosterone (TS) hormone concentration was lower (p