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Background: Recent advances have established that the pathogenic mechanisms of atherosclerosis are multifactorial, including inflammation, oxidative stress, dyslipidemia, and thrombosis.Buyang Huanwu decoction, which is the representative decoction of Yiqi Huoxue therapy, is widely used in the treatment of atherosclerosis.However, its concrete mechanisms on atherosclerosis have not been elucidated.Methods: We built atherosclerosis model in rabbits using inflated balloon inserted from right femoral artery to induce abdominal aortic wall injury.The atherosclerotic rabbits were fed with high-cholesterol diet for 8 weeks, and then intraperitoneally administrated Buyang Huanwu decoction in different dosages, simvastin and saline for 4 weeks, respectively.Results: Similar to effects of simvastin,Buyang Huanwu decoction reduced plague size, intimal thickness and the amount of macrophages while increased the size of connective tissue.Furthermore, Buyang Huanwu Decoction took part in multiple steps during the development of atherosclerosis through varieties of factors in molecular level including HDL, LDL, TC, 6-Keto-PGF1α, TXA2, TF, PAI-1, tPA, VWF:Ag, MDA, SOD, GSH-Px, CAT, ox-LDL, MPO, O2-,LOX-1, sVCAM, sICAM, sE-selectin, TNF-α, IL-6, IL-1β, MCP-1 and hs-CRR MMP-1 and TIMP-1.Conclusion:Buyang Huanwu Decoction played a role in the stabilization of unstable plaque to prevent or mitigate atherosclerosis by alleviating in lipid disorder, thrombosis, inflammation and oxidative stress.in addition, it also contributed to preserve the integrity of extracellular matrix.