Oxymatrine (OMT), an alkaloid extracted from Sophora japonica (kushen), is used to treat inflammatory diseases and various types of cancer in traditional Chinese medicine. However, the cellular and molecular mechanisms underlying the anti‑inflammatory activity of OMT remain poorly understood. The present study explored the protective effect of OMT on myocardial injury in rats with septic shock by inhibiting the activation of the janus kinase‑signal transducer and activator of transcription (JAK/STAT) signaling pathway. OMT treatment was found to significantly inhibit the activation of JAK2 and STAT3 in myocardial tissue. It also attenuated the expression of pro‑inflammatory cytokines, including interleukin‑1β and tumor necrosis factor‑α. In addition, OMT exhibited anti‑inflammatory properties as heart function and myocardial contractility was improved and pathological and ultrastructural injury was prevented in myocardial tissue induced by septic shock. The results indicate that OMT exhibits substantial therapeutic potential for the treatment of septic shock‑induced myocardial injury through inhibition of the JAK2/STAT3 signaling pathway.