Introduction: Smoking can affect hormone secretion; some of these effects are associated with important clinical implications. These effects are mainly mediated by the action of nicotine. Curcumin is a well known antioxidant agent. Aim of the work: To study the protective role of curcumin against nicotine induced toxic effects on the adrenal medulla. Methods: Thirty adult male mice were used and were divided into three groups (10 animals each): The first group (Group I) served as control group. The second group (Group II) received nicotine (2.5mg/kg b.wt., by subcutaneous injection ,daily for 4 weeks). The third group (group III) received curcumin (80 mg/kg b.wt) by intragastric intubation simultaneously along with nicotine for 4 weeks. Specimens of adrenal gland were processed for histological study by light and electron microscopes. Results: In nicotine treated mice, the chromaffin cells of the adrenal medulla showed increase in the cytoplasmic vacuolation, mitochondrial degeneration and decreased secretory granules. The nuclei showed abnormalities in the form of shrinkage, pyknosis and marked extended chromatin. These cellular changes have been found to be attenuated by curcumin. Conclusions: Curcumin administration may be protective for the chromoffin cells of the adrenal medulla against the toxicity of nicotine.