Objective To observe the effects of the traditional Chinese medicine (TCM), Wenyang-Yiqi recipe, on post-infarction heart failure in rats, and to investigate its pharmacological mechanism by AMPK-mediated mitochondrial autophagy. Methods A total of 100 healthy SPF rats were randomly divided into five groups (n = 20 per group): control group, sham-operated group, model group, TCM intervention group, and AMPK agonist group. The rat model of postinfarction heart failure was established by coronary artery ligation except for the control group and the sham operation group. Then, the TCM intervention group was given Wenyang-Yiqi recipe, 0. 10 mL/ kg by intragastric gavage once a day for four weeks, while the AMPK agonist group received the same dose of Wenyang-Yiqi recipe plus an intramuscular injection of EX229 at the same time. After 4 weeks of intervention, the left ventricular ejection fraction (LEVF) and heart/ body weight ratio of the rats were measured. The mitochondrial respiratory control ratio (RCR) was determined by a mitochondrial ventilator, and the protein expressions of p-AMPK/ AMPK, LC3II/ LC3I, PINK1 and Parkin were determined by western blotting assay. Results Compared with the control group, the heart/ body weight ratio of the model group and AMPK agonist group was increased, while the state3 respiratory rate and RCR were decreased. Compared with the model group, the heart/ body weight ratio of the TCM intervention group was decreased, while the state3 respiratory rate and RCR were significantly increased ( P <0. 05). Compared with the control group, the expression levels of p-AMPK/ AMPK, LC3II/ LC3I, PINK1 and Parkin in the myocardial tissue of the model group, TCM intervention group and AMPK agonist group were significantly increased, and compared with the model group, the expression levels of p-AMPK/ AMPK, LC3II/ LC3I, PINK1 and Parkin proteins in the TCM intervention group were significantly decreased ( P <0. 05). Conclusions The traditional Chinese medicine Wenyang-Yiqi recipe improves the myocardial function of rats with post-infarction heart failure, and the mechanism might be related to the inhibition of AMPK-mediated mitochondrial autophagy.