Abstract： Objective:To explore the role and preliminary mechanism of heparin-binding protein (HBP) in the development of acute pancreatitis (AP) through clinical analysis and animal models.Methods:(1) Clinical research: Blood samples were collected from AP patients admitted to the Second Affiliated Hospital of Anhui Medical University from January 1 to December 31, 2021 within 30 min of admission, including 20 patients with severe acute pancreatitis (SAP) and 20 patients with non-severe acute pancreatitis (NSAP). Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of HBP, syndecan-1 and hyaluronic acid (HA). Modified CT severity index (MCTSI), another 20 healthy volunteers were selected as controls (HC). Spearman correlation analysis was used to analyze the correlation between HBP and syndecan-1, HA and MCTSI. Receiver operating characteristic (ROC) curve was used to evaluate HBP to predict AP severity. (2)Animal experiment: The rat model of acute pancreatitis was prepared by intraperitoneal injection of L-arginine. In the normal control group (NC, n=8), the low molecular weight heparin (LMWH) intervention group ( n=8), and the acute pancreatitis group ( AP, n=8), the rats were euthanized 12 h later, and peripheral venous blood was collected to detect the levels of HBP, syndecan-1 and HA. Lung tissue and pancreas tissue were collected to observe the pathological damage, and the polysaccharide coating damage of vascular endothelial cells was observed under a fluoroscopy electron microscope. Results:The level of HBP at admission was significantly higher in the AP group than in the HC group, and the increase in the SAP group was more obvious. Correlation analysis showed that HBP was positively correlated with syndecan-1, HA and MCTSI. Animal studies found that the levels of HBP, syndecan-1 and HA in the AP group were significantly higher than those in the NC group. The pancreatic pathological score showed that the AP group was significantly increased, and the fluoroscopy electron microscope showed that the vascular polysaccharide coating was complete in the NC group, and the structure of the AP group was severely damaged. After LMWH intervention, the structure shedding and damage were significantly reduced, and the difference was statistically significant.Conclusions:HBP can promote the progression of AP, which is related to the destruction of the polysaccharide coating structure of endothelial cells and the increase of vascular permeability caused by HBP.