Objective: Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms. Methods: Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20 mu g/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1 beta, and interleukin (IL)-1 beta in pancreatic tissue was detected by Western blot and real-time PCR. Results: Dexmedetomidine at 20 mu g/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20 mu g/kg significantly down-regulated the expression of NLRP3, pro-IL-1 beta, and IL-1 beta in pancreatic tissue, but up-regulated the expression of NET in both mouse models. Conclusion: Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression. (C) 2018 Elsevier Inc. All rights reserved.