The pathophysiology of acute pancreatitis is characterized by a loss of intracellular and extracellular compartmentation, by an obstruction of pancreatic secretory transport and by an activation of pancreatic enzymes. In biliary acute pancreatitis, outflow obstruction with pancreatic duct hypertension and a toxic effect of bile salts contribute to disruption of pancreatic ductules, with subsequent loss of extracellular compartmentation. Alcohol induces functional alterations of plasma membranes and alters the balance between proteolytic enzymes and protease inhibitors, thus triggering enzyme activation, autodigestion and cell destruction. Once the disease has been initiated, the appearance of interstitial edema and inflammatory infiltration are the basic features of acute pancreatitis. The accumulation of polymorphonuclear granulocytes in pancreatic and extrapancreatic tissue, and the release of leukocyte enzymes play an essential role in the further progression of the disease and in the development of systemic complications. Activation of different cascade systems by proteolytic activity, and consumption of alpha 2-macroglobulin further characterize the severe clinical course of acute pancreatitis.