Objective To investigate the effects of polydatin (PD) on myocardial injury and Hippo-Yes associated protein (YAP) signaling pathway in rats with coronary heart disease (CHD).Methods The CHD rat model was constructed, and the successfully constructed rats were randomly divided into model group (CHD group), polydatin low-dose and high-dose groups (PD-L and PD-H groups), and high-dose polydatin + HiPO-YAP signaling pathway stimulator PY-60 group (PD-H+PY-60 group), with 18 rats in each group. Another 18 normal rats were selected as control group. The ultrasound echocardiography was applied to detect cardiac function. HE staining was applied to observe the pathological morphological changes of myocardial tissue. Masson staining was applied to observe the degree of myocardial fibrosis and the area of collagen fibrosis in rats. TUNEL staining was applied to observe cell apoptosis in myocardial tissue. Western blot was applied to detect the expression of B cell-lymphomatoma-2 associated X protein (Bax), caspase-3, p-YAP/YAP, and transcriptional coactivator with PDZ-binding motif (TAZ).Results Compared with the control group, the CHD group had abnormal myocardial cells, disordered myocardial fiber structure, obvious inflammatory cell infiltration and tissue edema, increased deposition of blue collagen fibers, and an increased proportion of myocardial collagen fibrosis area, the apoptosis rate of cells and the expression of Bax, Caspase-3, p-YAP/YAP, and TAZ increased, the LVEF, LVFS, and Em/Am levels decreased (P＜0.05). The morphology of myocardial cells in the PD-L and PD-H groups was relatively normal compared to the CHD group, with reduced cell necrosis, obviously reduced inflammatory cell infiltration and tissue edema, reduced deposition of blue collagen fibers, and reduced proportion of myocardial collagen fibrosis area. The apoptosis rate of cells and the expression of Bax, Caspase-3, p-YAP/YAP, and TAZ reduced, the LVEF, LVFS, and Em/Am levels increased (P＜0.05);the PD-H+PY-60 group showed more severe myocardial tissue damage, increased deposition of blue collagen fibers, and increased proportion of myocardial collagen fibrosis area compared to the PD-H group. The apoptosis rate of cells and the expression of Bax, Caspase-3, p-YAP/YAP, and TAZ increased, the LVEF, LVFS, and Em/Am levels decreased (P＜0.05).Conclusion Polydatin can improve myocardial injury in CHD rats, and its mechanism of action is related to the inhibition of the Hippo-YAP pathway