Background: Previous studies have described the protective effects of DADLE on myocardial injury in sepsis. Recently, autophagy has been shown to be an innate defense mechanism in sepsis-related myocardial injury. However, whether DADLE has an pro-autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of DADLE on the regulation of autophagy during sepsis. Methods: Male mice were subjected to LPS or vehicle intraperitoneal injection. After LPS injection, mice received either DADLE, Naltrindole or vehicle. ELISA and JC-1 were used to evaluate the level cTnl and Mitochondrial membrane potential. Cardiac ultrastructural and autophagosomes were visualized by transmission electron microscopy. The relative protein levels were analyzed by Western blot. Results: The results showed that treatment with DADLE both immediately or 4 h after LPS intraperitoneal injection could improve the survival rate of mice with endotoxemic. DADLE could ease myocardium ultrastructure injury induced by LPS, this cardioprotective effect was also seen in increased MMP levels, and decreased cTnl levels. Through observation of transmission electron microscopy and Western blot we have discovered that the amount of autophagosome and the expression of autophagy related protein LC3II, Beclinl were significantly increased with DADLE treatment. DADLE promoted LPS-induced autophagosome maturation as indicated by the increased LAMP-I protein level and decreased SQSTM1/p62 protein level. The selective 8-opioid receptor antagonist Naltrindole play an opposite effects. Conclusions: DADLE could improve the survival and protect myocardial dysfunction in mice with LPSinduced endotoxemia. This effect was related to the increase of autophagy. (C) 2017 Published by Elsevier Inc.