Objectives: Terminalia chebula Retzins (TC) has been used as a traditional remedy to treat gastrointestinal infectious and inflammatory diseases. However, the protective effect of TC on acute pancreatitis (AP) has not been studied. In this study, we tried to investigate the protective effect of TC water extract on cerulein-induced AP. Methods: To measure the protective effect of TC on AP, mice were injected with cerulein (50 μg/kg) hourly for 6 times. TC water extract (200 or 400 mg/kg) or saline was administered orally 1 h before the first injection of cerulein. The mice were sacrificed at 6 h after the last injection of cerulein. Pancreas tissues were taken for further analysis. Results: The administration of TC water extract showed an inhibitory effect on the increase of pancreas weight/body weight ratio and mitigated pancreatic damage in mice. Also, mRNA level of pro-inflammatory cytokines was inhibited by administration of TC water extract. Conclusion: Taken together, we found that administration of TC water extract ameliorates the severity of cerulein-induced AP, which suggests the potential to be an effective treatment on AP.