This study histologically and histochemically assess the effect of ethanol fruit extract of Phoenix dactylifera L. (EFPD) on the cerebral cortex of lead acetate exposed Wistar rats. Twenty rats were grouped into five groups (A to E, n=4). Group A (control) was administered distilled water (2 ml/kg), while groups B to E were treatment groups. Cerebral damage was induced in rats by the administration of lead acetate (120 mg/kg). Groups B, C, D and E were administered lead acetate (120 mg/kg) for a period of 3 weeks, after which groups C and D were administered EFPD (500 and 1000 mg/kg, respectively) and group E was administered dimercaptosuccinic acid (10 mg/kg) for 2 weeks. All administrations were via oral route, once daily. Microscopic examination of cerebral sections of lead acetate-treated rats revealed histo-architectural alteration; cortical degenerative changes, such as, necrosis, satellitosis, vacuolation and neuronal cytoplasmic shrinkage. However, administration of EFPD remarkably ameliorated lead acetate-induced cortical cerebral degenerative changes in the rats,in a dose dependently manner, as compared to the reference drug dimercaptosuccinic acid. Results suggest that EFPD is a potential therapeutic agent against lead acetate-induced cortical cerebral alterations in Wistar rats.