Background It is accepted that inflammatory cytokines play a key role in the development of acute pancreatitis,soblocking the initiation of inflammatory reactions may alleviate pathological changes of acute pancreatitis.We studied theregulatory effect of arsenic trioxide(As_2O_3)on apoptosis and oncosis of pancreatic acinar cells in vitro and in vivo and itstherapeutic effect on acute pancreatitis.Methods Pancreatic acinar cells were isolated by collagenase digestion method.Apoptosis and oncosis of isolatedpancreatic acinar cells were detected with Hoechst 33258+PI or Annexin V+PI double fluorescent staining.Amylase andlactate dehydrogenase release were measured.Acute pancreatitis was induced in Wistar rats by intraperitonealinjections of caerulein,and apoptosis was detected with terminal dUTP nick-end labeling method.Tumor necorsis factorα(TNF-α)mRNA,myeloperoxidase,nuclear factor-κB and histological grading of pancreatic damage were measured.Results There was an increased apoptosis but a decreased oncosis of pancreatic acinar cell after the treatment withAs_2O_3.The levels of lactate dehydrogenase and amylase release were markedly decreased in As_2O_3 treated group.Myeloperoxidase content,TNF-α mRNA level,nuclear factor-κB activation and pathological score in As_2O_3 treated groupwere significantly lower than in the untreated group.Conclusions As_2O_3 can induce apoptosis and reduce oncosis of pancreatic acinar cell,thus resulting in reducedrelease of endocellular enzyme of acinar cells,reduced inflammatory cell infiltration and decreased the production ofinflammatory cytokines,so that the outcome of alleviated pathological changes was finally achieved. Background It is accepted that inflammatory cytokines play a key role in the development of acute pancreatitis, soblocking the initiation of inflammatory reactions may alleviate pathological changes of acute pancreatitis. We studied theregulatory effect of arsenic trioxide (As_2O_3) on apoptosis and oncosis of pancreatic acinar cells in vitro and in vivo and it therapeutics effect on acute pancreatitis. Methods Pancreatic acinar cells were isolated by collagenase digestion method. Apoptosis and oncosis of isolated pancreatic acinar cells were detected with Hoechst 33258 + PI or Annexin V + PI double fluorescent staining. Amylase and lactate dehydrogenase release were measured. Acute pancreatitis was induced in Wistar rats by intraperitoneal injections of caerulein, and apoptosis was detected with terminal dUTP nick-end labeling method. Tumor necorsis factor α (TNF-α) mRNA, myeloperoxidase, nuclear factor-κB and histological grading of pancreatic damage were measured. Results There was an increased apoptosi s but a decreased oncosis of pancreatic acinar cell after the treatment withAs_2O_3.The levels of lactate dehydrogenase and amylase release were markedly decreased in As_2O_3 treated group. Myeloperoxidase content, TNF-α mRNA level, nuclear factor-κB activation and pathological score in As_2O_3 treated groupwere significantly lower than in the untreated group. Conclusions As_2O_3 can induce apoptosis and reduce oncosis of pancreatic acinar cells, resulting in reduced release of endocellular enzyme of acinar cells, reduced inflammatory cell infiltration and decreased the production of inflammatory cytokines, so that the outcome of alleviated pathological changes was finally achieved.