Previous studies have demonstrated that intravenous catalase infusion protects against the formation of pancreatic edema in cerulein-induced acute pancreatitis; however, polyethylene glycol (PEG)-conjugated catalase given as a bolus was not protective. Using radiolabeled catalase and PEG-catalase in subtherapeutic tracer doses, the pancreas tissue distributions of each were determined in rats with and without pancreatitis. Rats with cerulein-induced pancreatitis developed tissue concentrations of catalase within the pancreas that were three times those of PEG-catalase. The relatively low levels of PEG-catalase in the pancreas outside of the vascular compartment suggest that the failure to prevent edema formation may result from inability of PEG-catalase to reach extra vascular sites of injury because of the large molecular size.