Myocardial dysfunction is an important manifestation of sepsis. In addition, inactivation of the mitogen‐activated protein kinase (MAPK) signaling pathway has been reported to be beneficial in sepsis. The current study used gene expression profiling to demonstrate the overexpression of angiotensin II type 1 receptor (AT1R) and activation of the MAPK signaling pathway in sepsis. In this study, we used a rat model of sepsis established by cecal ligation and puncture to explore the mechanism of AT1R silencing in relation to the MAPK signaling pathway on myocardial injury. Various parameters including blood pressure, heart rate, and cardiac function changes were observed. Enzyme‐linked immunosorbent assay was used to measure the concentration of cardiac troponin T (TnT), cardiac troponin I (cTnI), and creatine kinase isoenzyme muscle/brain (CK‐MB). Myocardial enzyme, tissue antioxidant capacity, mitochondria swelling, and membrane potential were also detected. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining was applied to measure cell apoptosis, and messenger RNA and protein levels of apoptosis‐related proteins (Fas ligand [Fasl], B‐cell CLL/lymphoma [Bcl‐2], p53) were also detected. Initially, sepsis rats exhibited decreased survival rate, but increased ejection fraction (EF), heart rate, and concentrations of TnT, cTnI, and CK‐MB. Furthermore, decreased AT1R expression inactivated the MAPK signaling pathway (shown as decreased extracellular signal–regulated kinase and cyclic adenosine 3′,5′‐monophosphate response element binding protein expression), decreased EF, heart rate, and concentrations of TnT, cTnI, and CK‐MB, but increased sepsis rat survival rate. Eventually, decreased AT1R expression inhibited myocardial cell apoptosis (shown as decreased apoptosis rate and p53 and Fasl expression as well as increased Bcl‐2 expression). These findings indicated that AT1R silencing plays an inhibitory role in sepsis‐induced myocardial injury by inhibiting the MAPK signaling pathway.