OBJECTIVE： To study the effect of Wenyang zhenshuai granules on myocardial MEF2 in model rats with chronic heart failure （CHF）. METHODS： 10 rats were randomly selected in 60 rats as normal control group （normal saline）， the remaining 50 rats were randomly divided into model control group （normal saline）， positive control group [enalapril， 1.8 mg/（kg·d）]， Wenyang zhenshuai granules low-dose， medium-dose， high-dose groups [0.72， 1.44， 2.88 g/（kg·d）] after induced to CHF models by adriamycin， intragastrically administrated twice a day， for 4 weeks. After administration， heart function indexes [left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVSD） and left ventricular end-diastolic diameter （LVDD）] of rats in each group were detected， protein expressions of myocardial MEF2 and phosphorylated MEF2 （p-MEF2） and mRNA expression of MEF2 were determined. RESULTS： Compared with normal control group， LVEF， LVFS of rats in model control group and each administration group were significantly reduced （P＜0.05）， LVSD， LVDD were significantly increased （P＜0.05）； protein expression of myocardial p-MEF2 was significantly down-regulated （P＜0.05）， and there were no statistical significances in protein or mRNA expressions of MEF2 （P＞0.05）. Compared with model control group， heart function indexes of rats in each administration group were significantly improved （P＜0.05）；protein expression of myocardial p-MEF2 was significantly up-regulated （P＜0.05）， and there were no statistical significances in protein or mRNA expressions of MEF2 （P＞0.05）. CONCLUSIONS： Wenyang zhenshuai granule can antagonize the down-regulation effect of adriamycin-induced MEF2 protein phosphorylation， which may be one of the mechanisms of its treatment for CHF.