This study investigated the effects of sub‑chronic administration of lead (Pb) acetate on thiobarbituric acid reactive substances (TBA‑RS), total sulfhydryl content, protein carbonyl content, antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH‑Px]), acetylcholinesterase (AChE), and Na+K+‑ATPase in the cerebral structures of rats. Male Wistar rats aged 60 days were treated with saline (control group) or Pb (treatment group), at various doses, by gavage, once a day for 35 days. The animals were sacrificed twelve hours after the last administration, and the cerebellum, hippocampus and cerebral cortex were removed. The results showed that Pb did not alter the evaluated oxidative stress parameters. Furthermore, Pb (64 and/or 128 mg/kg) altered SOD in the cerebellum, cerebral cortex and hippocampus. Pb (128 mg/kg) altered CAT in the cerebellum and cerebral cortex and GSH‑Px in the cerebral cortex. Also, Pb (64 mg/kg and 128 mg/kg) altered GSH‑Px in the cerebellum. Moreover, Pb (128 mg/kg) increased AChE in the hippocampus and decreased Na+K+‑ATPase in the cerebellum and hippocampus. In conclusion, sub‑chronic exposure to Pb (occupational and environmental intoxication) altered antioxidant enzymes, AChE, and Na+K+‑ATPase, contributing to cerebral dysfunction.