Objective To investigate the function of JAK2-STAT3 signaling pathway in pancreatic injury and systematic inflammatory response in rats with acute necrotizing pancreatitis ( ANP) . Methods SD rats were randomly divided into the ANP group (n=48), ANP+JAK2 inhibitor Ruxolitinib group (ANP+R group, n=48), ANP+STAT3 inhibitot Stattic group (ANP+S group, n=48), ANP+Ruxolitinib+Stattic group (ANP+R+S group, n=48), and sham operation group (SO group, n=48). 5％ sodium taurocholate injection via retrograde pancreatobiliary duct was used to establish ANP model. Blood samples from abdominal aorta and pancreatic tissue were collected after 3 h, 6 h, 12 h and 18 h after modeling. Serum amylase (AMY) and tumor necrosis factor-α(TNF-α) and interleukin-4 (IL-4) were tested. JAK2 and STAT3 mRNA expression and protein expression of p-JAK2 and p-STAT3 in pancreas were examined by RT qPCR and western blot, respectively. Results AMY, TNF-α and IL-4 in plasma, and JAK2 mRNA, STAT3 mRNA, p-JAK2 protein and p-STAT3 protein at different time points in ANP group were all obviously higher than those in SO group(P<0. 05). Serum AMY, TNF-αand IL-4 in ANP+R group, ANP+S group and ANP+R+S group at different time points were lower than those in ANP group [12 h (5391 ± 1009),(6130 ± 1227),(4818 ± 992)U/L vs (8524 ± 1360) U/L;(147.25 ± 27.85),(156.25 ± 23.17),(127.87 ± 21.39) ng/L vs (187.58 ±20.09)ng/L;(45.89 ±16.95),(50.19 ±15.87),(38.87 ±14.03)ng/L vs (58.85 ±9.34)ng/L] . JAK2 mRNA and p-JAK2 protein,STAT3 mRNA and p-STAT3 protein in ANP+R group and ANP+R+S group at different time points were obviously lower than those in ANP group (12 h 0. 357 ± 0. 091 vs 0. 597 ± 0. 121,1. 115 ± 0. 203 vs 1. 217 ± 0. 213,0. 361 ± 0. 089 vs 0. 489 ± 0. 097,0. 965 ± 0. 189 vs 1. 128 ± 0. 217, 0. 362 ± 0. 092 vs 0. 597 ± 0. 121,1. 107 ± 0. 212 vs 1. 217 ± 0. 213,0. 297 ± 0. 087 vs 0. 489 ± 0. 097,0. 713 ± 0. 184 vs 1. 128 ± 0. 217). STAT3 mRNA and p-STAT3 protein in ANP+S group were obviously lower than those in ANP group(0. 319 ± 0. 107 vs 0. 489 ± 0. 097,0. 849 ± 0. 177 vs 1. 128 ± 0. 217), and the difference was statistically different (P<0.05). Conclusions The activation of JAK2-STAT3 signaling pathway in pancreas may play a key role in the pathogenesis of systematic inflammatory response in ANP.