Arteriosclerosis is a strictly age-dependent disease. In the present work, we studied the possible protective and curative roles of melatonin (Mlt) against the development of arteriosclerosis. The protective role was studied by giving Mlt at 2 dose levels (3 mg/kg and 30 mg/kg) for 6 weeks in normal adult male rats followed by induction of arteriosclerosis along with Mlt administration. It is found that Mlt decreased serum levels of calcium (Ca²⁺), triglycerides (TG) and increases high density lipoprotein-cholesterol (HDL-C) without significant effect on serum total cholesterol (TC) or low density lipoprotein-cholesterol (LDL-C) at 3 mg/kg dose level. However, at 30 mg/kg dose level a significant decrease in serum TG and increase in serum HDL-C was noticed without significant effect on serum TC, LDL-C or Ca²⁺ levels. Histo-pathological examination of blood vessel revealed no changes in the walls of blood vessels. The possible curative role of Mlt on arteriosclerosis was studied by treating arteriosclerotic rats with Mlt (3 mg/kg and 30 mg/kg) or with bezafibrate (Bzf) in order to compare the activity of Mlt against a common hypolipidemic drug in use. We found that both drugs lowered TC, TG, LDL-C, Ca²⁺ and increased HDL-C levels. Only Mlt at 30 mg/kg level was able to cause complete regression of the arteriosclerotic lesions. We concluded that Mlt has both protective and curative roles against arteriosclerosis and that it suppresses lipid levels and enhances Ca²⁺ level in normal rats. The high dose level of Mlt (30 mg/kg) is the most potent in treatment of experimental arteriosclerosis.