The effect of estradiol and progesterone therapy in serum and liver on the lipid profile of naturally menopausal albino rats of the Wistar strain of different age groups (12,18 and 24months) have been measured and compared with the age matched groups. Three months old rats were used as young controls. The aged rats were administered subcutaneous injection of 17-β-estradiol (0.1 μg/g body weight), progesterone (2.5 μg/g body weight) and similar concentrations of both in combined treatment for 1month and the level of triglycerides (TG), total lipids (TL), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were measured in serum and liver of 3, 12, 18 and 24months old control as well as treated groups. The results show that TG, HDL, VLDL levels were increased significantly by 71%, 155%, 54%, respectively in liver of 24months old rats by combination treatment when compared with age matched control animals. The levels of TL, TC and LDL were decreased by 20%, 31%, and 30%, respectively in serum of 12 months old rats in combination treatment group. The effect was more significant in 12 and 24 months old female rats with administration of estrogen and combined (EP) treatments. The results indirectly suggest that hormone replacement therapy (HRT) can reduce the risk of cardiovascular disease (CVD) thereby playing a cardio-protective role by restoring lipid and hormone levels to the similar levels as found in young female animals.