To investigate the protective effect of Suixin Capsules against myocardial fibrosis and the influence on 5'adenosine monophosphate-activated protein kinase(AMPK)/NF-E2-related factor 2(Nrf2) pathway in rats with heart failure(HF).Methods:Adriamycin(intraperitoneal injection) was used to induce HF in rats.Suixin Capsules(1.3 mg/kg，2.6 mg/kg，5.2 mg/kg) was given by gavage to rats in low-，medium-，and high-dose Suixin Capsules groups，respectively，and valsartan(13.35 mg/kg，i.g.，once a day) to rats in the valsartan group.The sham operation group and model group received the equivalent amount of normal saline.After 8 weeks，the cardiac function of rats was measured，and Masson staining of rat heart tissue was performed.The levels of reactive oxygen species(ROS)，glutathione(GSH)，superoxide dismutase(SOD)，AMPK，Nrf2，and heme oxygenase 1(HO-1) in the heart tissue were detected.Results:No obvious muscle fibers in the myocardium of the control group were observed，while a large amount of fibrous tissue between myocardial cells was found in the model group.Suixin capsules groups and the valsartan group showed different degrees of fibrous tissue proliferation in the myocardial cells，which was alleviated as compared with that in the model group，particularly in the valsartan group.The levels of left ventricular ejection fraction(LVEF)，left ventricular fractional shortening(LVFS)，GSH，SOD，AMPK，Nrf2，and HO-1 were lower and the levels of left ventricular systolic diameter(LVSD)，left ventricular end-diastolic diameter(LVEDD)，and ROS were higher in the model group than in the control group(P<0.05).Compared with the model group，Suixin Capsules groups and the valsartan group had higher levels of LVEF，LVFS，GSH，SOD，AMPK，Nrf2，and HO-1 and lower levels of LVSD，LVEDD，and ROS.The changes of the indexes were dose-dependent in the Suixin Capsules groups，but the effect of valsartan group was the most significant(P<0.05).Conclusion:Suixin Capsules inhibits myocardial fibrosis in HF rats by activating the AMPK/Nrf2 pathway.