【Abstract】Objective To investigate therapeutic effect and mechanism of hyperbaric oxygen and ulinastatin respectively or combinatively used to treat acute necrotizing pancreatitis (ANP). Methods One hundred and twenty SD rats were divided into 6 groups randomly: group of normal control, group receiving sham operation, group of untreated acute necrotizing pancreatitis (ANP group), group of acute necrotizing pancreatitis treated with hyperbaric oxygen (HBO group), group of acute necrotizing pancreatitis treated with ulinastatin (ULT group), and group of acute necrotizing pancreatitis treated with combined hyperbaric oxygen and ulinastatin (HBO+ULT group). The rat model of acute necrotizing pancreatitis was established according to Aho HJ et al. Concentrations of amylase, TNFα, TXB2 and 6ketoPGF1α in blood were measured through ELISA or radioimmunoassay. Changes of pancreatic histopathology were investigated. SPSS 10.0 was used in statistical analysis. Results The concentrations of amylase, TNFα, TXB2 in the ANPtreated groups were significantly lower than those of ANP group (P＜0.01) except for 6ketoPGF1α and the levels of amylase and TNFα of HBO group were strikingly higher than those in HBO+ULT group. Only the level of AMS was significantly different between ULT group and HBO+ULT group (P＜0.01). Pancreas histopathological scores(HS) and CD8 counts of ANP group were significantly higher than those the other three group, but CD4 counts and CD4/CD8 ratio were on the contrary (P＜0.05). HS of HBO and ULT were strikingly higher than those of HBO+ULT (P＜0.05).Conclusion ①Hyperbaric oxygen or ulinastatin can effectively decrease the blood levels of enzymes and cytokines and improve the pancreatic immunity. ②Hyperbaric oxygen in combination with ulinastatin are more effective than either of them in the treatment of ANP.