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Protective effect of Qishen Yiqi dropping pills on the myocardium of rats with chronic heart failure (CHF) was investigated. Sixty rats were divided into the sham operation (n=20), the model (n=20) and the Qishen Yiqi dropping pill treatment group (n=20) using the random table method. The treatment group received administration of Qishen Yiqi dropping pills. The model and the sham operation group were given the same amount of normal saline. Within 24 h after the last administration, the rats were sacrificed. The myocardia were used for reverse transcription-polymerase chain reaction, western blot analysis and histological examination. In the sham operation group, cardiomyocytes were stained evenly and arranged neatly and densely with clear structures. In the model group, the cell morphology was fuzzy, the myocytes were hypertrophied, the nuclear pyknosis was fragmented, the arrangement was disordered, the intercellular space was narrowed, and the cytoplasm was missing. The apoptosis rates of cardiomyocytes in the model and Qishen Yiqi dropping pill treatment group were significantly higher than that in the sham operation group (P&lt;0.05). The myocardial infarction areas in the model group and the Qishen Yiqi dropping pill treatment group were larger than that in the sham operation group (P&lt;0.05). The expression levels of transforming growth factor-β1, mothers against decapentaplegic homolog 2 (Smad2), Smad3, and caspase-3 messenger ribonucleic acids and proteins in the model group and the Qishen Yiqi dropping pill treatment group were higher than those in the sham operation group (P&lt;0.05). Qishen Yiqi dropping pills have an obvious myocardial protective effect on CHF rats, which may enhance the degree of myocardial fibrosis by inhibiting the TGF-β1/Smads pathway and improve cardiomyocyte apoptosis by suppressing the caspase-3 signaling pathway, thus protecting the myocardium.