Severe acute pancreatitis (SAP) is closely related to intestinal mucosal barrier dysfunction, in which intestinal epithelial mechanical barrier injury is the structural basis of SAP-related intestinal mucosal dysfunction. Among the molecular mechanisms of injury factors, inflammatory mediators and cytokines, produced by SAP waterfall inflammation, are the main factors of intestinal mucosal barrier injury. This article briefly describes the effects of SAP on intestinal mechanical barrier injury and its molecular mechanism in order to provide ideas for the treatment of SAP.