Abstract: Objective To observe the effects and mechanism of icariside Ⅱ（ICSⅡ） on myocardial ischemia-reperfusion injury in rats. Methods The rats were divided into sham operation（Sham） group,model（Model） group, ICSⅡ group, Selisistat（silent information regulator 1, SIRT1） inhibitor group, and ICSⅡ + Selisistat group. After pretreatment, the rat model of myocardial ischemia-reperfusion injury was established by ligation of anterior descending branch of left coronary artery. The changes of ventricular function were detected by ultrasound. HE staining was used to observe the changes of myocardial histopathology. The levels of serum interleukin-1β（IL-1β）, cardiac troponin I（cTnI）, and tumor necrosis factor（TNF-α） were measured by enzyme linked immunosorbent assay（ELISA）. Tunnel staining was used to detect myocardial apoptosis. Western blot was used to detect the expressions of SIRT1, acetylated-forkhead box O1（Ac-FOXO1）, Bcl-2 associated X protein（Bax）, cysteinecontaining aspartate-specific proteases-3（Caspase-3）, Cleaved-Caspase-3 and B-cell lymphoma-2（Bcl-2） proteins in myocardial tissue. Results Compared with Sham group, the left ventricular end-diastolic pressure（LVEDP） in model group increased, the mean arterial pressure（MAP）, left ventricular systolic pressure（LVSP）, left ventricular ejection fraction（LVEF） and left ventricular fraction shortening（LVFS） decreased, the levels of cTnI, TNF-α and IL-1β increased, the apoptosis rate increased, the expression of SIRT1 decreased, the expression of Ac-FOXO1 increased, the expressions of Bax and Caspase-3 proteins in myocardial tissue increased, the expression of Bcl-2 protein decreased, and the differences were statistically significant（P＜0.05）. Compared with the Model group, the LVEDP in ICSⅡ group decreased, the MAP, LVSP, LVEF and LVFS increased, the levels of cTnI, TNF-α and IL-1β increased, the apoptosis rate decreased, the expression of SIRT1 increased, the expression of Ac-FOXO1 decreased, the expressions of Bax and Cleaved-Caspase-3 proteins in myocardial tissue decreased, the expression of Bcl-2 protein increased, and the differences were statistically significant（P＜0.05）; the LVEDP in Selisistat group increased, the MAP, LVSP and LVEF decreased, the levels of cTnI, TNF-α and IL-1β increased, the apoptosis rate increased, the expression of SIRT1 decreased, the expression of Ac-FOXO1 increased, the expressions of Bax and Cleaved-Caspase-3 proteins in myocardial tissue increased, the expression of Bcl-2 protein decreased, and the differences were statistically significant（P＜0.05）. The LVEDP, cTnI, TNF-α, IL-1β, apoptosis rate, the expression of Ac-FOXO1, the expressions of Bax and Cleaved-Caspase-3 proteins in myocardial tissue of ICSⅡ + Selisistat group were lower than those of Selisistat group, while the MAP, LVSP, LVEF, LVFS, the expressions of SIRT1 and Bcl-2 were higher than those of Selisistat group, and the differences were statistically significant（P＜0.05）. Conclusion IcarisideⅡ pretreatment can alleviate myocardial inflammatory injury and improve ventricular function in rats with myocardial ischemia-reperfusion injury, which may be related to activation of SIRT1-FOXO1 pathway.