Effects of FUT-175, a novel synthetic protease-inhibiting agent, on various models of experimental acute pancreatitis were examined. FUT-175 infused i.v. at a dose range of 5-50 micrograms/kg/min inhibited the increase in plasma trypsin activity and reduced the mortality of rabbits in trypsin-induced acute pancreatitis in a dose-dependent manner. Increase in serum amylase activity and pancreatic tissue lesion were attenuated in rabbits. In addition, FUT-175 infused i.v. at a dose range of 1-50 micrograms/kg/min reduced the mortality of rats in experimental acute pancreatitis produced by trypsin and endotoxin. FUT-175 infused i.v. at a dose range of 1-100 micrograms/kg/min protected the dogs from the increase in plasma trypsin activity and hypotension and shock induced by trypsin, well-known characteristics of acute pancreatitis. These results suggest that FUT-175 is beneficial as a therapeutic agent of acute pancreatitis.