Histamine-2 (H2) receptor antagonists (H2RAs) are administered orally or parenterally for the treatment of gastro-duodenal ulcers, gastric hypersecretory diseases, and gastro-esophageal reflux disease. In Japan, H2RAs are frequently used in patients with acute pancreatitis to reduce the secretion of pancreatic juice. Ranitidme is a specific competitive H2RA with immunomodulatory and anti-inflammatory properties. The efficacy of ranitidine for the treatment of acute pancreatitis has not been sufficiently evaluated. In this study, we evaluated the efficacy of ranitidine for the treatment of caerulein-induced pancreatitis as a model of acute pancreatitis. The effect of ranitidine on pancreatitis was assessed by examination of serum amylase and lipase levels, pancreatic edema, and histological changes. The prophylactic administration of ranitidine significantly reduced elevated serum amylase and lipase levels. At a histological level, ranitidine also reduces pancreatic edema, vacuole formation in pancreatic acinar cells, and inflammatory cell infiltration in the pancreas. An increase in the level of interleukin-10 in pancreatic tissue was also observed. These findings show that ranitidine accelerates the recovery of caerulein-induced pancreatitis. This effect may be due, at least in part, to increased anti-inflammatory cytokine production in pancreatic tissue and its protective role against local injury.