Objective To investigate the effects of thrombopoietin on adriamycin-induced cardiomyocyte apoptosis in rats with heart failure based on the TGF-β1 / Smad3 signaling pathway. Methods Rats were randomly divided into control, model, treatment, and inhibitor groups. Rats in the model, treatment, and inhibitor groups were injected with doxorubicin to establish a rat heart failure model. Rats in the treatment group were intraperitoneally injected with 5 μg / kg thyroperoxidase (TPO) daily and rats in the inhibitor group were intraperitoneally injected with 1. 2 mg daily / kg SB431542. TUNEL staining, immunofluorescence, and western blot were used to detect the cell apoptosis of cardiomyocytes, and the expressions of caspase-3, TGF-β1, and p-Smad3. Results Compared with the control group, the cell apoptosis rate of myocardial tissue cells in the model group was significantly increased and the expressions of TGF-β1, p-Smad3 and caspase-3 were significantly increased. Compared with the model group, the apoptosis rate of myocardial tissue in the treatment and inhibitor groups and the expressions of TGF-β1, p-Smad3, and caspase-3, were significantly decreased. The differences were statistically significant compared with the model group ( P < 0. 05). Conclusions TPO reduced the apoptosis rate of cardiomyocytes induced by doxorubicin in rats. The mechanism may be related to the inhibition of the TGF- β1 / Smad3 signaling pathway