Oxygen free radicals mediate an important step in the initiation of experimental acute pancreatitis. These reactive oxygen metabolites are generated at an early stage of the disease. However, the source of the enhanced production of oxygen radicals still remains unclear. Experimentally, the effectiveness of scavenger treatment varied from one model to another, the differences depending on the experimental model and not on the form of pancreatitis that was induced. In most studies the experimental animals were pretreated before inducing acute pancreatitis. This does not mirror clinical reality, since patients are admitted to the hospital after the onset of the disease. It was shown in cerulein-induced pancreatitis, however, that scavenger treatment also mitigated the pancreatic tissue damage after induction of acute pancreatitis. Moreover, antioxidant treatment also attenuated the extrapancreatic complications, thus improving the final outcome of the disease. Initial indirect observations also suggest that in human acute recurrent and chronic pancreatitis oxygen free radicals are generated and add to the damage. Well-defined controlled clinical trials involving patients suffering from acute pancreatitis are therefore needed to validate the role of oxygen radicals in this disease.