Objective: To explore the role and mechanism of Akkermansia muciniphila (A. muciniphila) in severe acute pancreatitis in mice. Methods: C57BL/6J male mice were randomly divided into four groups: control group， model group， live A. muciniphila group and pasteurized A. muciniphila group. The animal model of severe acute pancreatitis was established by intraperitoneal injection of caerulein combined with lipopolysaccharide. Mice were given live A. muciniphila or pasteurized A. muciniphila at 200 μL/mouse (5×109 CFU/mL) by intragastric gavage every day 10 days before the first caerulein stimulation. The intestinal permeability and the expression of tight junction proteins were examined. Additionally， the pancreatitis markers (pancreatic edema， serum amylase level， serum lipase level and histomorphology) and the levels of inflammatory factors (proinflammatory cytokines and NF-κB) were investigated. Results: The expression of tight junction proteins， goblet cells and mucus layer were both increased in live A. muciniphila group and pasteurized A. muciniphila group. Notably， the live A. muciniphila exhibited optimal protective effect on intestinal barrier function. However， the modulation of A. muciniphila on severe acute pancreatitis was not insufficient. Conclusion: Live A. muciniphila and pasteurized A. muciniphila both protect the intestinal barrier function； however， they could not alleviate severe acute pancreatitis in experimental mice.