Abstract: Severe acute pancreatitis (SAP) is a common acute abdominal condition, with pancreatic encephalopathy (PE) being one of its complications, characterized by central nervous system (CNS) lesions when pancreatic inflammation occur. The blood-brain barrier (BBB), serving as a physical and biochemical barrier between peripheral circulation and the CNS, plays a crucial role in maintaining the stable microenvironment of the CNS. Damage to the BBB can lead to secondary cerebral edema in SAP patients. Investigating the relationship between BBB and SAP can provide new insights into the prevention and treatment of PE. This review summarized the cellular composition, basic structure, and physiological functions, as well as the current research status of inflammatory factors and gut microbiota in the course of PE in adjusting BBB, exploring the patterns of BBB changes during the onset and progression of PE.