Aim To study the protective effect and molecular mechanism of polydatin on myocardial cell injury after acute myocardial infarction in rats. Methods SD male rats were randomly divided into Sham group, AMI group, polydatin group, polydatin + ZnPP group. The latter 3 groups were established by ligating the left anterior descending coronary artery. Polydatin is administered by 40 mg per day, and the heme oxygenase 1 (HO-1) inhibitor ZnPP is intraperitoneally injected with 20 mg per day. On the 8th day after model establishment, the left ventricular ejection fraction (LVEF), the maximum increase and decrease rate of left ventricular pressure (±dp/dtmax), serum myocardial injury index, myocardial infarct size, oxidative stress index and nuclear factor E2 related factor 2 (Nrf2)/HO-1 expression in each group were measured. Results Compared with Sham group, LVEF, ＋dp/dtmax, －dp/dtmax and the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in myocardial tissue of AMI group significantly decreased, the infarct size, the contents of lactate dehydrogenase (LDH), phosphocreatine kinase (CK), phosphocreatine kinase isoenzyme (CK-MB) in serum and the content of MDA and the expression of Nrf-2, HO-1 inmyocardial tissue significantly increased(P<0.05); compared with AMI group LVEF, ＋dp/dtmax, －dp/dtmax and the contents of SOD, GSH-Px and the expression levels of Nrf-2, HO-1 in myocardial tissue of polydatin group were significantly increased, the infarct size, the contents of LDH, CK, CK-MB in serum and the content of MDA inmyocardial tissue were significantly decreased(P<0.05); compared with polydatin group, LVEF, ＋dp/dtmax, －dp/dtmax and the contents of SOD, GSH-Px in myocardial tissue of polydatin+ZnPP group significantly decreased, and the infarct size, the contents of LDH, CK, CK-MB in serum and and the contents of MDA in myocardial tissue significantly increased(P<0.05). Conclusion Polydatin can alleviate myocardial cell injury after acute myocardial infarction in rats, and this effect is partially mediated by the activation of Nrf2/HO-1 pathway.