BACKGROUNDAbdominal paracentesis drainage (APD) is a safe and effective strategy for severe acute pancreatitis (SAP) patients. However, the effects of APD treatment on SAP-associated cardiac injury remain unknown.AIMTo investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms.METHODSSAP was induced by 5% sodium taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after SAP induction. Morphological staining, serum amylase and inflammatory mediators, serum and ascites high mobility group box (HMGB) 1, cardiac-related enzymes indexes and cardiac function, oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats. Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined.RESULTSAPD treatment improved cardiac morphological changes, inhibited cardiac dysfunction, decreased cardiac enzymes and reduced cardiomyocyte apoptosis, proapoptotic Bax and cleaved caspase-3 protein levels. APD significantly decreased serum levels of HMGB1, inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury. Furthermore, the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis.CONCLUSIONAPD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress, which may be a novel mechanism behind the effectiveness of APD on SAP.