Matrine, an alkaloid isolated from the traditional Chinese medicine Sophora flavescens AIT has exhibited a number of therapeutic effects on cardiovascular and liver diseases. The purpose of the present study was to investigate whether matrine has a protective effect on heart failure in rats. Coronary artery ligation was used to induce a heart failure (CHF) model in rats. Four weeks following the procedure, the rats were treated with different doses of matrine for one month. Histopathological examination demonstrated that matrine treatment alleviated myocardial hypertrophy and cardiac fibrosis in failing hearts. Furthermore, matrine administration also inhibited the increase of plasma aspartate amino transferase, creatine phosphokinase and lactate dehydrogenase levels in CHF rats. The rats with heart failure exhibited a significant reduction in ejection fraction and fractional shortening, as well as an increase in the left ventricular end systolic dimension, and matrine attenuated this decline in heart function. Further investigation demonstrated that matrine treatment also inhibited the upregulation of Bax and increase in the Bcl‑2 expression in the failing hearts. Furthermore, the upregulation of β3-adrenoreceptor (AR) and endothelial nitric oxide synthase proteins following heart failure were also attenuated by matrine. In conclusion, matrine had a preventive role in heart failure in rats at least in part by inhibiting myocardial apoptosis and the β3-AR pathway.