〔Abstract〕 Objective To investigate the protective effect of emodin on cardiac function in rats with myocardial ischemia-reperfusion injury(MIRI) by activating Nrf2/ARE/HO-1 signaling pathway. Methods Rats were randomly divided into Sham group, MIRI group, Positive control group, emodin 20, 40, 60 mg/kg group, then MIRI model of rats were established, ECG detection of left ventricular end-diastolic pressure(LVEDP), left ventricular systolic pressure(LVSP), maximal rise/fall rate of left ventricular pressure change(±dp/dtmax), myocardial infarct size was measured, biochemical analyzer was used to detect the concentration of serum creatine kinase(CK), lactate dehydrogenase(LDH) and troponin(cTnI), myocardial tissue pathological changes were observed by HE staining, cleaved Caspase-3 positive cell rate was detected by immunohistochemistry, the content of myeloperoxidase(MPO), malondialdehyde(MDA), Superoxide dismutase(SOD) was measured by kits, Western blot was used to detect the protein levels of nuclear factor E2 related factor 2(Nrf2) and heme oxygenase 1(HO-1). Then rats were randomly divided into Sham group, MIRI group, emodin group and emodin+ML385 group, rats in emodin+ML385 group were treated by Nrf2 inhibitor ML385, and changes of cardiac function, pathological changes, inflammation and oxidative stress were detected. Result Compared with Sham group, the rats in MIRI group had elevated LVEDP and LVSP, decreased ±dp/dtmax, increased myocardial infarct size, increased serum CK, LDH, and cTnI concentrations, obvious pathological changes in tissues, and the positive cell rate of cleaved Caspase-3 increased, the MPO and MDA cotent increased, SOD content decreased, protein levels of Nrf2 and HO-1 increased. Emodin treatment played a protective role for cardiac function damage, Nrf2 signaling pathway was further activated. ML385 treatment significantly inhibited emodin induced protective effect of cardiac function. Conclusion Emodin can alleviate MIRI injury, and its mechanism is related to the activation of Nrf2/ARE/HO-1 signaling pathway.