Lead acetate has potential toxic health effects on humans. Information from epidemiological studies proposed that lead environmental exposure may have resulted in reproductive and developmental toxicity. Luteolin is an antioxidant that has antioxidant properties. Aim: to assess the protecting role of luteolin against toxic effects of lead acetate in testis. Methods: The study was performed on 40 adult male albino rats that had been divided equally into 4 groups, 10 rats for each group. Group I (a) (Negative control group) given only regular diet and tap water. Group I (b) (Luteolin control group): given Luteolin (50 mg/kg/day) once daily by oral gavage for 4 weeks; Group ІІ : Lead group: received 50 mg/kg/day in 0.5 ml distilled water byoral gavage for 4 weeks ; Group ІIІ (Lead - Luteolin group): received Lead and Luteolin with the same mentioned doses. After 4 weeks, 24 hours after the last dose, we measured: 1-Total mRNA expressions using RT-PCR of: Nrf2, Keap1, NQO1, and HO-1. 2-Testicular oxidative stress markers: MDA, SOD, and GPx activity. 3- Testis Inflammatory Cytokines: TNF-α. and IL-6. Hematoxylin and Eosin and immunohistochemical examination of testis were evaluated. Results: In the lead treated rats, there was an elevation in MDA. Lead caused decrease in tissue SOD and GPx; TNF-alpha and IL-6 increased in testis tissues together with elevation of the expression of (Nrf2, Keap1, NQO1, and HO-1). lead induced histological damages and strong immunoreaction decreased by co-treatment of luteolin. Conclusion: luteolin improved testis function and histology against toxicity of lead acetate.