〔Abstract〕 Objective To investigate the effect of salidroside(Sal) on ischemia reperfusion(IR) in isolated rat heart and explore the underlying mechanisms on endoplasmic reticulum stress(ERS) and apoptosis. Methods The isolated rat hearts underwent Langendorff perfusion subjected to IR. After ischemia for 45 min and reperfusion for 2 h, the isolated rat hearts were randomly divided into four groups(n=10): Control group, Sal treatment group(Sal), ischemia reperfusion group(IR) and Sal treatment with ischemia reperfusion group(IR+Sal). Myocardial infarct size was detected by TTC staining. Lactate dehydrogenase(LDH) activity in the coronary flow was determined by ELISA. The cardiac function was evaluated by left ventricular peak systolic pressure(LVSP) and left ventricular end diastolic pressure(LVEDP). The expressions of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax),protein kinase R-like endoplasmic reticulum kinase(PERK), C/EBP homologous protein(CHOP) and activating transcription factor 6(ATF6) were detected by Western blot, and apoptosis was observed by TUNEL staining. Results There was no significant difference in all indexes between Sal group and Control group. Compared with Control group, the infarct size and LDH activity in the coronary flow increased in IR group. The LVSP value decreased, and the LVEDP value increased. The expression of Bax and the TUNEL-positive cells increased, while the expression of Bcl-2 decreased. Meanwhile, the expressions of ERS related proteins including PERK, CHOP and ATF6 also increased. Compared with IR group, the infarct size and LDH activity in the coronary flow increased in IR+Sal group. The LVSP value increased, and the LVEDP value decreased. The expression of Bax and the TUNEL-positive cells decreased, while the expression of Bcl-2 increased. In addition, the expressions of PERK, CHOP and ATF6 decreased. Conclusion Sal can improve myocardial IR injury by inhibiting ERS and apoptosis in isolated rat hearts.