Objective To investigate the effect of sodium tanshinone II A sulfonate (STS) on cardiomyocyteapoptosis in rats with dilated cardiomyopathy (DCM), and its potential mechanism of action. Methods DCM rats wererandomly divided into DCM, STS-L, STS-M, STS-H, Carvedilol (CAR), and control groups,12 rats in each group. Leftventricular internal diameter at end-systole (LVIDs) and left ventricular internal dimension at end-diastole (LVIDd), andleft ventricular ejection fraction (LVEF) were measured by echocardiography. Pathological injury of myocardial tissues wasobserved using hematoxylin and eosin, and Masson trichrome staining. Tumor necrosis factor-α (TNF-α) and interleukin-6(IL-6) levels were quantified using enzyme-linked immunosorbent assays, while apoptosis in cardiomyocytes was detectedusingTUNEL staining. Expressions of phosphorylated phosphatidylinositol 3 kinase ( p-PI3K), phosphorylated proteinkinase B (p-Akt), Bax, caspase-3, and Bcl-2 were detected by immunoblotting and immunohistochemistry. Results Compared with the control group, the DCM group exhibited increased LVIDs and LVIDd, decreased LVEF, increasedmyocardial histopathologic scores and percentage of cardiac collagen fibers, increased serum levels of TNF-ɑ and IL-6, andincreased apoptosis index (AI) in cardiomyocytes ( P < 0. 05). Compared with the DCM group, the STS and CAR groupsexhibited decreased LVIDs and LVIDd, increased LVEF, decreased myocardial histopathologic scores and percentage ofcardiac collagen fibers, decreased serum levels of TNF-ɑ and IL-6, and decreased apoptosis index(AI) in cardiomyocytes( P < 0. 05). Compared with the control group, the expressions of p-PI3K, p-Akt, and Bcl-2 proteins were decreased inthe DCM group, while expressions of caspase-3 and Bax proteins were increased ( P < 0. 05). Compared with the DCMgroup, the expressions of p-PI3K, p-Akt, and Bcl-2 proteins in STS and CAR groups were increased, while expressions ofcaspase 3 and Bax proteins were decreased ( P < 0. 05). Conclusions STS may inhibit cardiomyocyte apoptosis in DCM rats by activating PI3K/ Akt signaling and exert protective effects.