Abstract: Objective　To investigate the effects of extracellular ATP (eATP) -P2X7R -NLRP3 axis on the inflammation and fibrogenesis of chronic pancreatitis (CP), and the therapeutic effect of ATP inhibitor carbenoxolone (CBX) on CP. Methods　C57BL/6 mice (male, 6-week-old) were randomly divided into 5 groups: normal group, model group, CBX low, medium and high-dose groups (25, 50 and 100 mg/kg, respectively). After the mouse models of CP were established, the three CBX groups were intraperitoneally injected with corresponding doses of drugs. The mice were killed by cervical dislocation 24 h after the last drug injection. Pancreatic histopathological changes were evaluated by HE staining. eATP levels were measured by the luminescence ATP detection assay. The protein expressions of P2X7R, NLRP3 and Caspase-1 were measured by immunofluorescence staining, and the expressions of P2X7R, NLRP3, Caspase-1 and Pannexin-1 (PAN-1) mRNA were detected by real-time fluorescent polymerase chain reaction (qPCR). Results　Under light microscope, the normal group showed tightly distributed cells in murine pancreas without fibrosis and inflammatory cell infiltration. Compared with the normal group, the intercellular space of the pancreatic tissue, atrophy of the pancreatic acinus, hyperplasia of the collagen fibers and infiltration of a large number of inflammatory cells among fibers were elevated in model group with an increased histopathological score (P＜0.01). Compared with the model group, the content of collagen and the degree of inflammatory cell infiltration were reduced with a decreased histopathological scores in CBX groups. The eATP level was significantly higher in model group than that of the normal group (P＜0.01). After 2 weeks of treatment, the levels of eATP in murine pancreatic tissue were lower in CBX medium and high-dose groups than that of model group. Compared with the normal group, the protein expressions of P2X7R, NLRP3 and Caspase-1 were significantly increased in the model group (P＜0.01). Compared with the model group, these 3 protein expressions were down-regulated in CBX treatment groups, in which a significant effect was found in the CBX medium and high-dose groups (P＜0.05). Results of qPCR showed that the expression of PAN-1 mRNA was significantly up-regulated in model group compared with that of normal group. Compared with the model group, the levels of PAN-1 mRNA were reduced in CBX medium and high-dose groups (P＜0.01). Conclusion　In the course of CP, the eATP level is significantly increased, and then activates the P2X7R, which can accelerate the NLRP3 inflammasome assembly and aggravates pancreatic fibrosis. CBX can down-regulate the expressions of P2X7R, NLRP3 and Caspase-1, alleviate the injury and fibrosis of pancreatitis and consequently play a therapeutic role.