Abstract: OBJECTIVE To study the effect and mechanism of rhamnetin on myocardial ischemia-reperfusion injury in rats. METHODS One hundred SD rats were randomly divided into normal group, model group, rhamnetin low(50 mg·kg^-1), medium(100 mg·kg^-1) and high(200 mg·kg^-1) dose group, 20 rats in each group. Except for the normal group, rats in each group were prepared by ligation of the left anterior descending coronary artery. Each group of rhamnoflavin was intragastrically administered at the corresponding dose once a day for 20 consecutive days. The MAP, HR, and LVSP levels in rats were detected by the BL-420 signal acquisition system. The expression of CK-MB, Mb, cTn I, IL-6, IL-1β, iNOS and TNF-α in serum was detected by ELISA. The expression of Bcl-2, Bax, caspase-3, caspase-9, TLR4, P-NF-κB p65 and MIP-2 in cardiomyocytes was detected by Western blotting. The content of MDA and SOD in cardiomyocytes was detected by kits. The expression of Ki67 in cardiomyocytes was detected by immunohistochemistry, and myocardial damage was observed by HE staining. RESULTS Compared with model group, in the administration group, MAP, HR, and LVSP were significantly increased, CK-MB, Mb, and cTn I expressions were significantly reduced, Bax expression was significantly down-regulated, Bcl-2 expression was significantly up-regulated, SOD content was significantly increased, MDA content was significantly reduced, and Ki67-positive ratio was significantly decreased, myocardial cells returned to normal morphology, caspase-3 and caspase-9 expressions were significantly down-regulated, IL-6, IL-1β, iNOS, TNF-α levels were significantly reduced, and TLR4, P-NF-κB p65 and MIP-2 expressions were significantly reduced. CONCLUSION Rhamnetin mainly protects myocardial cells from myocardial ischemia-reperfusion by reducing oxidative stress, inducing cell proliferation, inhibiting apoptosis and slowing down inflammatory response.