Chronic lead (Pb) poisoning is one of the greatest public health risks. The nervous system is the primary and most vulnerable target of Pb poisoning. Selenium (Se) has been shown to be a potential protection against heavy metal toxicity through anti-inflammatory and antioxidant properties. Therefore, the present study aimed to elucidate the possible protective role of Se in ameliorating the effects of Pb on rat cerebral structure by examining oxidative stress and markers of apoptosis. The rats were divided into 6 groups: control group, Se group, low Pb group, high Pb group, low Pb + Se group, high Pb + Se group. After the 4-week experiment period, cerebral samples were examined using biochemical and histological techniques. Pb ingestion especially when administered in high doses resulted in cerebral injury manifested by a significant increase in glial fibrillary acidic protein, malondialdehyde (MDA) marker of brain oxidation and DNA fragmentation. Moreover, Pb produced alteration of the normal cerebral structure and cellular degeneration with a significant reduction in the total number of neurons and thickness of the frontal cortex with separation of meninges from the cerebral surface. There was also a decrease in total antioxidant capacity. All these changes are greatly improved by adding Se especially in the low Pb + Se group. The cerebral structure showed a relatively normal histological appearance with normally attached pia and an improvement in neuronal structure. There was also a decrease in MDA and DNA fragmentation and an increase TAC. Selenium is suggested to reduce Pb-induced neurotoxicity due to its modulation of oxidative stress and apoptosis.