【Abstract】Objective To investigate the effects and mechanism of inhibition dynaminrelated protein 1 (Drp1) through the phosphatidylinositol3kinase (PI3K)/ protein kinase B (AKT) pathway on sevoflurane (Sev) postconditioning cardiomyocyte apoptosis in diabetic mellitus (DM) rats. Methods Rats were divided into Sham group, ischemia/reperfusion (I/R) group, I/R+DM group, IR+DM+Sev group, IR+DM+Sev+ Mdivi1 group and IR+DM+Mdivi1 group. The rat model of DM was established by intraperitoneal injection of streptozotocin. The myocardial I/R model was established by ligation. Sev was inhaled after ischemia or mdivi 1, an inhibitor of drp1, was intraperitoneally injected. The infarct volume, myocardial tissue damage, myocardial cell apoptosis level, and PI3K/AKT pathway level in each group were compared. Results The levels of cTnI, CKMB, and apoptosis index in the I/R group were significantly higher than those in the Sham group and PI3K and AKT levels were significantly lower than those in the Sham group (P＜005). The levels of cTnI, CKMB, and apoptosis index in the I/R+DM group were significantly higher than those in the I/R group and PI3K and AKT levels were significantly lower than those in the I/R group (P＜005). The levels of cTnI, CKMB and apoptosis index in IR+DM+Sev group and IR+DM+Mdivi1 group were significantly lower than those in IR+DM group and PI3K and AKT levels were significantly higher than that in I/R group (P＜005). The levels of cTnI, CKMB and apoptosis index in IR+DM+Sev+Mdivi1 group were significantly lower than those in IR+DM+Sev group and IR+DM+Mdivi1 group while PI3K and AKT levels were significantly higher than IR+DM +Sev group and IR+DM+Mdivi1 group (P＜005). Conclusion Inhibiting Drp1 can inhibit the myocardial cell apoptosis of myocardial I/R model of DM rats by promoting the PI3K/Akt pathway, thereby promoting the protective effect of Sev on myocardial I/R injury in DM rats.