Background: Cardiovascular disease (CVD) is one of the leading causes of death worldwide and is more prevalent in post-menopausal women. Monocyte chemo-attractant protein-1(MCP-1) is a chemokine that attracts monocytes/macrophages to sites of inflammation and play a role in development of atherosclerosis. Objective: This study aimed to explore the effects of ovariectomy (Ovx) as a model of menopause on the serum level of MCP-1 in high fat diet induced atherogenesis and clarify the modulatory effects of moderate exercises on the serum level of MCP-1 in this model. Animals and methods: 96 female albino rats divided equally into 4 groups, each is subdivided equally into 2subgroups subgroup (Ia): non ovx ,sedentary, fed standard diet for 10 weeks, subgroup (Ib): non ovx ,sedentary, fed high fat diet for 10 weeks. Subgroup (IIa) ovx sedentary, fed standard diet for 10 weeks subgroup (IIb): ovx, sedentary fed high fat diet for 10 weeks. Subgroup (IIIa): non ovx ,exercised and fed standard diet for 10 weeks. subgroup (IIIb) non ovx ,exercised and fed high fat diet for 10 weeks. Subgroup (IVa): ovx ,exercised and fed standard diet for 10 weeks. subgroup (IVb) ovx ,exercised and fed high fat diet for 10 weeks. Results: in ovx obese sedentary rats, there was a significant (p <0.001) increase in MCP-1,Lipid profile, Atherogenic indices, Platelets activation percentage, Total leucocytic counts, Differential monocyte counts, and Interleukin 8 and aortic thickness versus lean subgroup. Swimming exercise showed significant (p <0.001) reductions in the above parameters, associated with significant increase in the serum HDL level in ovx obese exercised subgroup versus ovx obese sedentary subgroup. Conclusions: MCP-1 level increased in obesity and menopause leading to development of atherosclerosis and these changes could be reversed by adaptive moderate exercises.