Aim To explore the effect of adiponectin (APN) on acute alcohol induced myocardial injury in mice and related mechanism, and to provide experimental basis and new ideas for the prevention and treatment of acute alcoholic myocardial injury and alcoholic cardiomyopathy. Methods 8 week old C57BL/6J male mice were randomly divided into normal control group (n＝10) and normal model group (n＝15). 8 week old male SPF homozygous adiponectin knockout (APN－/－) mice were randomly divided into APN－/－ control group (n＝10) and APN－/－ model group (n＝15). Model groups were given intraperitoneal injection of ethanol 3 g/(kg·d), control groups received normal saline intraperitoneal injection. 4 groups of mice were normal feeding, drinking water. After 3 days, the indicators were monitored:the general condition of mice was observed, serum lactate dehydrogenase (LDH) and N-terminal B type natriuretic peptide (NT-proBNP) were detected, cardiac structure and function index were detected by mouse heart ultrasonic machine, myocardial cell apoptosis was detected by TUNEL and the activity of Caspase 3 was determined, myocardial tissue HE staining and Masson staining were prepared, myocardial tissue homogenate reactive oxygen species (ROS) content, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected, Western blot was used to detect NADPH oxidase 2 (NOX2) protein expression in myocardial tissue. Results Compared with normal control group, ejection fraction of normal model group decreased significantly (P＜0.01); serum LDH and plasma NT-proBNP concentration of normal model group were increased by 1.98 times, 5.13 times (P＜0.01); HE staining and Masson staining showed myocardial structure and muscle fiber changes, collagen fibers increased, collagen volume fraction (CVF) value increased 2.63 times in normal model group (P＜0.01); the activity of Caspase 3 in myocardial tissue increased 2.58 times (P＜0.01), positive myocardial cell apoptosis increased 12.67 times by TUNEL in normal model group (P＜0.01); ROS content and MDA content in myocardium were increased by 1.68 times, 2.87 times (P＜0.01), SOD activity increased 2.92 times in normal model group (P＜0.01); the expression of NOX2 protein increased 1.87 times in normal model group (P＜0.01). Compared with control group, the above indicators in APN－/－ model group were significantly increased (P＜0.01). Compared with normal group, serum LDH and plasma NT-proBNP concentration were increased by 1.30 times, 1.25 times in APN－/－ model group (P＜0.01); HE and Masson staining showed the myocardial structure and muscle fiber changes, collagen fibers increased, CVF value increased by 1.55 times in APN－/－ model group; the activity of Caspase 3 in myocardial tissue increased 1.66 times (P＜0.01), the myocardial cell apoptosis ratio was 1.64 times higher in APN－/－ model group (P＜0.01); ROS content and MDA content in myocardium were increased by 1.42 times, 1.39 times (P＜0.01), SOD activity decreased 28% in APN－/－ model group (P＜0.01), the expression of NOX2 protein increased 1.44 times in APN－/－ model group (P＜0.01). Conclusion Adiponectin can reduce acute alcoholic myocardial injury in mice, and its mechanism may be related to the inhibition of NOX2 protein expression and the effect of anti-oxidative stress.