Acute pancreatitis (AP) is an acute inflammatory disease of the exocrine pancreas. In spite of the pivotal role of the endocrine pancreas in glucose metabolism, the impact of impaired glucose tolerance on AP has not been fully elucidated. A meta-analysis of seven observational studies showed that type 2 diabetes mellitus (DM) was associated with an increased risk of AP. The increased risk of AP shown in the meta-analysis was independent of hyperlipidemia, alcohol use and gallstones. Anti-diabetic drugs including incretins might increase the risk of AP, but no intervention trials have confirmed this. Although a controversial finding, DM seems to be associated with severe attacks and organ failure in AP. We analyzed the results of a nationwide epidemiological survey of AP in Japan. We studied the impact of pre-existing DM on the clinical course of AP in 1954 cases for which information on DM status was available at the onset of AP. The prevalence of DM in AP patients (12.8%) was higher than that in the general population in Japan (10.5%). AP patients with DM had higher morbidity of cardiovascular and renal failure than those without DM. About 35% of the idiopathic AP patients with DM had renal failure. The mortality of AP patients with DM (4.0%) was higher than that of AP patients without DM (1.7%). If stratified by etiology, idiopathic, but not alcoholic or biliary, AP patients with DM were predisposed to increased mortality (9.7%). In conclusion, impaired glucose tolerance might have an impact on the development and clinical outcome of AP. However, the impact might depend on the cause of hyperglycemia, the condition of DM including severity, duration and treatment, and the characteristics of the AP patients including age, etiology and comorbidity.