Acute pancreatitis sometimes develops to severe condition with a variety of clinical manifestations and high mortality. Autodigestion of the pancreas, secondary to the activation of digestive enzymes, plays a major role in the pathogenetic mechanism of acute pancreatitis. To improve the mortality and complication rates, appropriate treatments based on the precise prediction of disease severity are required. To this end, the early administration of protease inhibitors has commonly been employed for the therapy of acute pancreatitis in Japan. However, a number of clinical trials have failed to show the clinical effects of protease inhibitors, H2 receptor antagonist and somatostatin analogue on the treatment of acute pancreatitis. To evidence the therapeutic value of these agents for acute pancreatitis, well-organized clinical studies will be required.