The protective effect of melatonin against the damage of nicotine on the brain in ovariectomized female rats (OVX) was investigated. Cigarette smoking is common in societies worldwide and has been identified as injurious to human health. The data revealed that nicotine,a major  component of cigarette smoke ( at a dose of 2 mg/ KG b.wt.) resulted in a significant increase in total proteins, lipid peroxides (LPO), total cholesterol and phospholipids, and a significant decrease in acetylcholenesterase activity (AChE) and glutathione content (GSH). Melatonin administration at dose (5 mg/kg b.wt.)to nicotine treated rats showed significantly ameliorated changes in total proteins,  acetylcholenesterase (AChE) , glutathione content (GSH) , lipid peroxides (LPO) , total cholesterol (TC) and phospholipids (Ph). The obtained results suggest that the protective effect of melatonin is mediated through decreased  oxidation of lipids , thus minimizing the risk posed by nicotine .