Abstract: The aim of this study was to explore the protective mechanism of dexmedetomidine (DEX) on myocardial injury induced by LPS in rats. Firstly, thirty healthy male SD rats, weighing 180-220 g, were randomly and evenly divided into three groups:control group (CON), lipopolysaccharide group (LPS) and DEX group (DEX), with 10 rats in each group. The sepsis model was established by intraperitoneal injection of 10 mg·kg^-1 LPS in rat of LPS, and DEX group; and in DEX group, the rats were pretreated with 30 μg·kg^-1 DEX 30 minutes before LPS injection. Four hours later, the abdominal cavities of rats were opened by dissection, blood samples were collected from abdominal aorta, and at the same time, myocardial tissues were obtained. Serous creatine kinase (CK) and lactic dehydrogenase (LDH) levels were measured. HE staining was used to detect myocardial pathological changes in rats. Western blot was applied to detect the expression of NOX2, NLRP3, IL-1β and IL-18 in myocardial tissue. Results were as follows:Compared with CON group, serous CK and LDH levels in LPS group increased significantly (P<0.01 or P<0.001); histopathological observation revealed that myocardial tissue injury was aggravated, and myocardial fibrous septum was widened. The expression of NOX2 and downstream NLRP3 inflammatory body-related proteins were increased significantly (P<0.05, P<0.01 or P<0.001). The above indexes in DEX group were significantly lower than those in LPS group (P<0.05, P<0.01 or P<0.001), and there was no significant difference between DEX group and CON group (P>0.05).The results showed that DEX inhibited the activation of NLRP3 inflammatory bodies by reducing the activity of NOX2. Finally, the expression of inflammatory factors was reduced to improve myocardial injury induced by sepsis in rats.