AIM: To investigate the preventive and therapeutic effects of Hawthorn flavone on hyperlipidemia and atherosclerosis rats. METHODS: The atherosclerosis model was established by high fat diet plus vitamin D2. The blood lipid levels, heart index, atherosclerosis index (AI1, AI2) and coronary heart index were measured in each group. The histopathological changes of aorta were observed by oil red O staining, HE staining and Masson staining. ELISA experiments were used to detect IL-6, ICAM-1, MCP-1 and VCAM-1 protein level. RESULTS: Compared with normal group, total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), heart index, atherosclerosis index (AI1, AI2) and coronary index in atherosclerosis model group were significantly increased (P<0.01), while high density lipoprotein cholesterol (HDL-C) was significantly decreased (P<0.01). The pathological score of aorta and the degree of fibrosis were significantly increased (P<0.01). Compared with model group, TC, TG, LDL-C, heart index, atherosclerosis index (AI1, AI2) and coronary heart index were significantly decreased (P<0.01), and high-density lipoprotein cholesterol (HDL-C) was significantly increased (P<0.01) in medium, high dose hawthorn flavonoids and atorvastatin groups. The pathological score of aorta significantly decreased and the degree of fibrosis significantly improved (P<0.01). The variation trend of blood lipid levels in hyperlipidemia rats is basically consistent with atherosclerotic rats. Meanwhile, compared with model group, the medium, high dose hawthorn flavonoids and atorvastatin groups could significantly inhibit the expression levels of IL-6, MCP-1, ICAM-1 and VCAM-1 adhesion molecules (P<0.01). CONCLUSION: The hawthorn flavone can inhibit the formation of aortic endothelial atherosclerotic plaque, reduce the degree of fibrosis and inflammation of atherosclerotic plaque in rats, and achieve the purpose of anti-atherosclerosis. Meanwhile, the hawthorn flavone has the effect of regulating blood lipid.