Acute necrotizing pancreatitis is still a fatal disease. Pancreatic necrosis might be, in part, a result of infarction due to ischemia with vasospasm and an increase in intravascular coagulability. Synthetic antiproteases have a broad inhibitory action on pancreatic enzymes, the coagulation system, the complement system and the production of proinflammatory cytokines. Therefore, antiproteases have been expected to prevent necrotic changes in the pancreas and to reduce the mortality rate. However, the clinical efficacy of antiproteases is still a matter of controversy. Unfortunately, an antiprotease cannot easily reach the pancreas when administered intravenously because of its pharmacokinetic characteristics and impaired microcirculation. Administration through a catheter placed in one of the arteries which supplies the inflamed area of the pancreas, dramatically increases the concentration of the antiprotease in the pancreas. Clinical studies of continuous regional arterial infusion of a protease inhibitor have been conducted in Japan and have demonstrated the possible therapeutic efficacy of the new treatment in severe acute pancreatitis.