Lead (Pb) is one of the most common toxic heavy metals. It is a well‐known testicular toxicant. Selenium nanoparticles (SeNPs) are a more effective form of elemental selenium that reduces drug‐induced toxicities. This study aimed to study the possible ameliorating effect of SeNPs on the toxicological and morphological changes in testes of lead acetate intoxicated rats. The study was conducted on 40 adult male albino rats divided into four groups; control, SeNPs‐treated, lead acetate‐treated, lead acetate and SeNPS treated groups. The concurrent treatment of lead acetate‐exposed rats with SeNPs (0.1 mg/kg/ day) for 12 weeks significantly lowered the blood and testicular lead levels, increased serum testosterone, and decreased luteinizing hormone and follicle‐ stimulating hormone to approach control values. In addition, it improved the histopathological, and ultrastructural alterations of the testes and improved the immunohistochemical expression of the c‐kit. This was accompanied by maintenance of the testicular oxidant/antioxidant balance and reversing the lead‐induced disrupted calmodulin‐related genes expression in testicular tissue in the form of downregulation of CAMMK2 and MAP2K6 and upregulation of CXCR4 genes. There was a strong positive correlation between testicular malondialdehyde and MAP2K6 expression level as well as a strong positive correlation between CXCR4 gene expression and the C‐kit area %. In conclusion, SeNPs can be considered as a potential therapy for a lead‐induced testicular injury.