To observe the intervention effect of Qishen Taohong Granule(QSTH) on myocardial remodeling in stress-loaded heart failure mice at different stages [2 weeks and 4 weeks after transverse aortic constriction(TAC)] and the effect on autophagy-related miRNA.Methods:A total of 90 C57 mice were randomly divided into model group(M group)，QSTH group(T group)，QSTH+rapamycin group(TR group)，QSTH+3-methyladenine group(T3M group)，enalapril group(E group)，and sham operation group(S group).Two and four weeks after operation，cardiac function was monitored.Hematoxylin and eosin(HE) staining，Masson staining，apoptosis detection and quantitative analysis were performed，and the formation of autophagosomes in left ventricular tissues was observed under transmission electron microscopy.The miRNA sequencing and verification were performed for the left ventricular tissues in the S，M and T groups.Results:At 2 weeks after operation，T group was superior to the other groups in improving left ventricular ejection fractions(LVEF)(P<0.05)，and at 4 weeks after operation，T group and E group were superior to the other groups in improving LVEF.Except S group，the geometric deformation of the heart and cardiac hypertrophy were observed in the other groups.The myocardial fiber apoptosis in T group and E group was lower than that in the other groups(P<0.05).Except S group，there were autolyfollicles，autophagosomes and autolysosomes in other groups，and myofibrocytes were arranged disorderly.Compared with that of S group，the sequencing of M group indicated that metabolic pathways and lysosomal pathways were closely related to cardiac autophagy and their enrichment factors were higher，showing a significant difference.Compared with the conditions in M group，mammalian target of rapamycin(mTOR) and lysosomal pathways in T group were enriched significantly，which were closely related to autophagy.Conclusion:QSTH improves the myocardial remodeling in stress-loaded heart failure mice，and the mechanism may be miRNA regulating autophagic flux to produce the protective effect.