Objective To determine the effects of guanxinning (GXN),a traditional Chinese medicine, in mice with chronic heart failure (CHF) and to explore the mechanisms involved, with particular reference to cardiomyocyte apoptosis and related signaling pathways, to provide experimental evidence for the clinical use of GXN. Methods A mouse CHF model was established by surgical aortic arch constriction and mice with successfully-induced CHF were randomly allocated to a model control group, a low-dose (600 mg/ kg) GXN group, a high-dose (1,200 mg/ kg) group, and a positive control group (administered 12. 5 mg/ kg captopril). In addition, sham-operated mice were used as a control group. The survival rate was monitored during the experiment. Ultrasonography was performed after 3, 6, and 9 weeks of the study, when the ejection fraction (EF) of the mice was measured. At the end of the study, the mice were sacrificed and their hearts collected. Myocardial apoptosis was quantified using the TUNEL staining, the mRNA expression of BAX and BCL2 were quantified using RT-PCR, and the protein expression levels of PI3K, p-AKT, and BAX/ BCL2 were measured using a fully-automated protein analyzer. Results The survival rate was 50% in the model control group, 60% in the lowdose GXN group, and 70% in the high-dose GXN group. Compared with the sham surgery group, the EF in the model group was significantly lower after 3, 6, and 9 weeks, while GXN administration induced to varying degrees of improvement. There was more myocardial apoptosis in the model than in the sham group, and GXN reduced this. The myocardial mRNA expression of BAX in the model group was significantly higher, and that of BCL2 was lower, which was consistent with the protein expression levels, and the PI3K and p-AKT protein levels were also significantly higher. Compared with the model group, the mRNA expression of BAX and the protein expression levels of PI3K and p-AKT were lower in the myocardium of high-dose GXN-treated mice. Conclusions GXN improves the survival rate and cardiac function of mice with CHF. The mechanism may be involved with the upregulation of the PI3K/ AKT/ BAX signaling pathway, which reduces cardiomyocyte apoptosis, thereby ameliorating the signs of heart failure in CHF mice.