AIM: To investigate the preventive and therapeutic effects of Hawthorn flavone on hy-perlipidemia 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 cor-onary heart index were measured in each group. The histopathological changes of aorta were ob-served by oil red O staining, HE staining and Mas-son staining. ELISA experiments were used to de-tect IL-6, ICAM-1, MCP-1 and VCAM-1 protein level. RESULTS: Compared with normal group, total cho-lesterol (TC), triglyceride (TG), low density lipopro-tein (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 sig-nificantly 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 lipo-protein cholesterol (HDL-C) was significantly in-creased (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 hyperlip-idemia rats is basically consistent with atheroscle-rotic 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 forma-tion of aortic endothelial atherosclerotic plaque, re-duce the degree of fibrosis and inflammation of atherosclerotic plaque in rats, and achieve the pur-pose of anti-atherosclerosis. Meanwhile, the haw-thorn flavone has the effect of regulating blood lip-id.