Objective: To analyze perioperative serum high mobility group box-1 protein (HMGB1) levels in patients with acute cholangitis and its clinical significance. Methods: 118 cases of choledocholithiasis with acute cholangitis were retrospectively analyzed, admittd in Minhang Hospital from Jan 2017 to Dec 2017. Enzyme linked immunosorbent assay (ELISA) was used to detect serum HMGB1 levels before and after ERCP. The relationship between serum HMGB1 levels and severity of the disease was analyzed. Results: The serum HMGB1 levels in the healthy controls, mild cholangitis group, moderate cholangitis group and severe cholangitis group were(1.74±0.79) μg/L, (9.19±4.86) μg/L, (12.62±4.13) μg/L, (18.02±3.84) μg/L, respectively. The serum HMGB1 levels were significantly different in these four groups (F=63.348, P<0.05). The serum HMGB1 levels in the three groups after ERCP were significantly lower than those before ERCP(t=10.978, t=35.682, t=42.649; P<0.05). The serum HMGB1 levels were positively correlated with WBC, CRP, total bilirubin, direct bilirubin and alanine aminotransferase. Conclusion Serum HMGB1 levels were significantly higher in patients with acute cholangitis, and the more serious the disease, the higher the HMGB1 levels. After ERCP, serum HMGB1 levels were significantly lower than before. HMGB1 is an effective parameter for evaluating the severity of acute cholangitis.