We studied the involvement of ascitic fluid on the systemic effects of experimental acute pancreatitis. This has been achieved by comparing the effectiveness of either peritoneal lavage or lymphatic ligature on preventing changes in systemic vascular permeability. Three hours after induction of pancreatitis, we found increases in vascular permeability in the pancreas, lung, and intestine. Both peritoneal lavage and lymphatic ligature were able to prevent the changes observed in the lung and intestine and the increases on plasma levels of lipase and amylase, suggesting a similar involvement for lymphatic draining and peritoneal absorption pathways. In addition, we evaluated the effect of intraperitoneal deposition into health rats of pancreatitis-associated ascitic fluid collected from rats with experimental acute pancreatitis. A significant increase in plasma amylase and lipase levels could be observed but no changes in vascular permeability were found. Altogether, these results indicate that transperitoneal absorption of toxic mediators from the ascitic fluid is not enough to explain the systemic damage induced by acute pancreatitis.