Objective To investigate the effect of AG490 on the apoptosis of pancreatic acinar cells and expression of apoptosis gene FasL and Bcl-2 in rat model of severe acute pancreatitis (SAP). Methods Seventy-two healthy Wistar rats were randomly divided into control group (n=24), SAP group (n=24) and AG490 group (n=24). Heart blood samples were taken to detect serum amylase at 6 h, 12 h and 24 h after operation in three groups. Pancreatic tissue were observed under light microscope to analyze pathological changes and pathological scores. The index of pancreatic acinar cell apoptosis was detected by TUNEL. The expressions of FasL and Bcl-2 mRNA in pancreatic tissue was detected by RT-PCR. Results Compared with control group, the damage of pancreatic tissue was gradually increased, the serum level of amylase significantly increased (P＜0.01), the index of pancreatic acinar cell apoptosis increased, the expression of FasL mRNA was significantly increased, the expression of Bcl-2 mRNA was significantly decreased (P＜0.05 or P＜0.01) in SAP group. Compared with SAP group, the pancreatic injury was improved significantly, the serum amylase significantly decreased ( P＜0.01), the apoptosis index rate of pancreatic acinar cells was increased, the expression of FasL mRNA was significantly increased, and the expression of Bcl-2 mRNA was significantly decreased (P＜0.05 or P＜0.01) in AG490 group. Conclusion The inhibition of the JAK/STAT3 signaling pathway may regulate the apoptosis-related gene to increase the apoptosis of pancreatic acinar cells, thereby reducing the reaction and pathological damages of acute pancreatitis.