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Aliskiren is a direct renin inhibitor. It counteracts renin-angiotensin system and is used to treat hypertension. This study aims to evaluate the effect of aliskiren on the progression of atherosclerosis in domestic rabbits. Twenty-one local domestic rabbits were divided into three groups each group had special dietary regimen for 8 weeks: Group I (normal control), Group II (atherogenic control) and Group III (2% Cholesterol+ aliskiren 40mg/kg/day orally). Blood samples were collected at the end of experiment (8 weeks) for measurement of serum lipid profile, plasma high sensitive C-reactive protein (hs-CRP), plasma malondialdehyde (MDA) and plasma reduced glutathione (GSH). Immunohistochemical analysis including vascular cell adhesion molecule-1 (VCAM-1); monocyte chemoattractant protein-1 (MCP-1); tumor necrotic factor-'(TNF-'); and interleukin'17 (IL-17). Histopathologic assessment of aortic atherosclerotic changes were also performed. Compared to normal control group, there is a significant increase in the level of lipid profile, hs-CRP (134.1±1.2 ug/L), and malondialdehyde (0.561±0.136 umol/L) in the atherogenic diet group, while GSH was significantly reduced (0.58±0.024 mmol/L) at (p'0.05). Immunohistochemical analysis showed that expression of aortic VCAM-1; MCP-1; TNF-'; and interleukin'17 were significantly increased in atherogenic control group compared to normal control group (p< 0.001). In addition, animals on atherogenic diet have significant atherosclerotic lesion compared to normal control group. Aliskiren group appears to have no significant effect on lipid profile compared to atherogenic …