Lead acetate (PbAc) 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. The study aimed to assess the protective role of luteolin against the toxic effects of PbAc in testis. The study was performed on 40 adult male albino rats divided equally into 4 groups, 10 rats for each group. Group I (Negative control group) was given only a regular diet and tap water. Group IІ (Luteolin control group) was given Luteolin (50 mg/kg/day) once daily by oral gavage for 4 weeks. Group ІІІ (PbAc group) received 50 mg/kg/day in 0.5 ml distilled water by oral gavage for 4 weeks. Group IV (PbAc-Luteolin group) received PbAc and Luteolin with the same 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 the testis were evaluated. In the PbAc-treated rats, there was an elevation in MDA. PbAc caused a decrease in tissue SOD and GPx; TNF-α and IL-6 increased in testis tissues together with elevation of the expression of (Nrf2, Keap1, NQO1, and HO-1). PbAc-induced histological damage and strong immunoreaction for alpha-smooth muscle actin (α-SMA) and glucose-regulated protein 78 (GRP 78), decreased by co-treatment of luteolin. In conclusion luteolin improved testis function and histology against toxicity of PbAc.