Background: A serious health issue that raises the possibility of strokes and cardiovascular illness is atherosclerosis. The main risk factor for atherosclerosis occurrence is the high fat diet (HFD).The elevated blood lipid levels lead to endothelial dysfunction with subsequent sub endothelial accumulation of lipids and formation of plaques. Aim: To clarify the preventive effect of atorvastatin and sesame oil on aortic atherosclerosis induced by HFD in rats. Materials and methods: Thirty two animals were split into four groups: Group I (control group), group II (atherosclerosis group): Rats were given a high-fat diet (HFD) till the end of the eighth week in order to induce atherosclerosis, group III (atorvastatin group): Rats were administered both HFD and atorvastatin orally at a dose of 20 mg/kg/day for eight weeks, and group IV (atorvastatin + sesame oil group): Rats supplemented with HFD in addition to atorvastatin (20 mg/kg/day) and 10% sesame oil for the same duration. Blood samples were withdrawn to assess the serum level of Cholesterol, Triglyceride, low-density lipoproteins (LDL), and high-density lipoproteins (HDL). The aortas were promptly excised and prepared for histological and immunohistochemical examination. Results: Atherosclerosis group revealed a substantial rise (P ≤ 0.05) in cholesterol, LDL, and triglyceride serum measurements, while HDL quantity displayed a major decrease. The H&E stained sectors presented increased aortic wall thickness with intimal projection into the lumen. Foam cells appeared in the tunica media. Additionally, there was marked reduction in endothelial nitric oxide synthase (eNOS) immune expression, but there was powerful tumor necrosis factor -α (TNFα) immune reactivity in the aortic layers. Treatment with atorvastatin improves the serum lipid profile levels, the histological structure of the aortic wall, as well as the immunohistochemical results. However, combination therapy of atorvastatin and sesame oil displayed better results. Conclusion: The present investigation provides biochemical, histological, and immunohistochemical support of the significant prophylactic impact of atorvastatin and sesame oil combination in improving lipid profiles, amelioration of aortic damage, reduction in inflammatory indicators, and thus atherosclerosis limitation.