Abstract: Objective To investigate the effects of salidroside (Sal) on mitochondrial autophagy in ischemic cardiomyopathy (ICM) rats by modulating the PTEN-induced kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) signaling pathway. Methods Thirty SD rats were randomly divided into control group, model group, low-dose Sal group, high-dose Sal group, mitochondrial autophagy inhibitor (Mdivi-1) group and high-dose Sal + Mdivi-1 group, with five rats in each group. The ICM rat model was established. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameters (LVIDs) were analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase (CK) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Hematoxylin and eosin (HE) staining was performed to observe pathological changes in myocardial tissue, and transmission electron microscopy was used to examine mitochondrial structure. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Western blot analysis was conducted to determine the expression levels of microtubule-associated protein light chain 3 (LC3), Beclin1, p62, PINK1 and Parkin in myocardial tissue. Results Compared with the control group, the model group showed more severe myocardial tissue and mitochondrial damage. The LVEF, LVFS, SOD and p62 levels in the model group were significantly lower than those in the control group, while the LVIDd, LVIDs, LDH, cTnI, CK, NT-proBNP, ROS, MDA, LC3II/LC3I, Beclin1, PINK1 and Parkin levels were significantly higher (P<0.05). Compared with the model group, the low-dose and high-dose Sal groups exhibited reduced myocardial and mitochondrial damage. The LVEF, LVFS, SOD, LC3II/LC3I, Beclin1, PINK1 and Parkin levels in the low-dose and high-dose Sal groups were significantly higher than those in the model group, while the LVIDd, LVIDs, LDH, cTnI, CK, NT-proBNP, ROS, MDA and p62 levels were significantly lower (P<0.05). Compared with the model group, the Mdivi-1 group showed more severe myocardial and mitochondrial damage. The LVEF, LVFS, SOD, LC3II/LC3I, Beclin1, PINK1 and Parkin levels in the Mdivi-1 group were significantly lower than those in the model group, while the LVIDd, LVIDs, LDH, cTnI, CK, NT-proBNP, ROS, MDA and p62 levels were significantly higher (P<0.05). Compared with the low-dose Sal group, the high-dose Sal group demonstrated further improvement in myocardial and mitochondrial damage. The LVEF, LVFS, SOD, LC3II/LC3I, Beclin1, PINK1 and Parkin levels in the high-dose Sal group were significantly higher than those in the low-dose Sal group, while the LVIDd, LVIDs, LDH, cTnI, CK, NT-proBNP, ROS, MDA and p62 levels were significantly lower (P<0.05). Mdivi-1 significantly inhibited mitochondrial autophagy and suppressed the activation of the PINK1/Parkin signaling pathway and the improvement in cardiac function induced by Sal (P<0.05). Conclusion Sal may improve myocardial injury in ICM rats by activating the PINK1/Parkin signaling pathway and promoting mitochondrial autophagy.