Background: Lead exposure can cause adverse effects on the reproductive system. This study aimed to evaluate the protective and therapeutic effects of vitamin E on lead-induced pituitary and gonadal dysfunctions and the possible mechanisms underlying these effects. Material and methods: 104 Albino Wistar adult rats were divided into four groups: group I: 12 rats received vehicle of lead and 12 rats received vehicle of vitamin E; Group II: 40 rats subdivided into 2 subgroups: Group IIa: 20 rats injected with lead acetate (10 mg/kg/day 5 times/week, i.p. for 6 weeks) and Group IIb: 20 rats injected with lead as previous then stopped for 6 weeks; Group III: 20 rats injected with lead acetate as previous followed by oral administration of vitamin E (50 mg/kg/day 5 times/week); Group IV: 20 rats received vitamin E simultaneously with lead acetate as previous. At the end of the experiment the animals were scarified and blood samples were collected for measurement of gonadotrophic, gonadal hormones, malondialdehyde (MDA), total antioxidant capacity (TAC) and caspase 3 by ELISA kits. The pituitary gland, testes, and ovaries were processed for histopathological examination. Results: Lead administration significantly decreased the plasma levels of gonadotrophic, and gonadal hormones, and TAC but significantly increased the plasma levels of MAD and caspase 3. Meanwhile, vitamin E administration with or after lead exposure significantly increased gonadotrophic, gonadal hormones and TAC and markedly decreased MAD and caspase 3. Conclusion: Vitamin E has protective and therapeutic effects on lead-induced gonadal dysfunction. This effect mediated by inhibition of oxidative stress and apoptosis.