. This study aimed to investigate the effect of miR-183-5p on sepsis-induced cardiac dysfunction and understand the underlying mechanism. The cecal ligation and puncture method (CLP) was used to estab-lish an animal model of sepsis. The results demonstrated that compared with the control group, CLP+miR-183-5p mimic/inhibitor NC group exhibited focal degeneration and necrosis of myocardial cells, infiltration of inflammatory cells, a dramatically increased apoptosis level of myocardial cells and cardiac ultrasonic parameters decreased evidently. In addition, with the remarkably increased protein expression of IRS1, the protein expressions of p-PI3K and p-mTOR rose in myocardium, while those of LC3II and Beclin declined. Moreover, compared with CLP+miR-183-5p mimic NC group, the myocardial cells showed a pathological improvement tendency, the apoptosis level and the protein expressions of IRS1, p-PI3K and p-mTOR in myo-cardium dropped markedly, LVAW; d, LVAW; s, LVPW; d and EF, and LC3II and Beclin associated with autophagy evidently rose in CLP+miR-183-5p mimic group. Compared with CLP+miR-183-5p inhibitor NC group, the indicators of CLP+miR-183-5p inhibitor group tended to deteriorate. LPS was utilized to induce myocardial cell injury in in vitro experiments. It was found that miR-183-5p mimic down-regulated the pro-tein expressions of IRS1, p-PI3K, p-Akt and p-mTOR, and up-regulated the expressions of LC3II and Beclin, while miR-183-5p inhibitor had the opposite effect. In a word, miR-183-5p enhances autophagy by targeting IRS1 to regulate the PI3K/Akt/mTOR signaling pathway. Therefore, miR-183-5p can be of therapeutic impor-tance for the regulation of sepsis-induced cardiac dysfunction.