AbstractAlthough its exact nature is still unknown, acute pancreatitis progresses with a local production of inflammatory mediators, eventually leading to systemic inflammatory response syndrome. Knowing that almost all pancreatic mediators released from the pancreas to the bloodstream may pass through the liver before their dilution in the systemic circulation, it would be reasonable to assume a determinant role for this organ in the development of the inflammatory response associated with acute pancreatitis. Thus, recent studies have shown the involvement of the liver in the complex network of events triggering the multiorgan dysfunction associated with the disease. Once pancreatic mediators reach the liver, they strongly activate Kupffer cells, the resident macrophages, greatly amplifying the release of cytokines into the bloodstream and thus contributing to the systemic manifestations of acute pancreatitis. Altogether, these results show that the pancreas is not the only source of mediators that trigger the deleterious effects of acute pancreatitis, but that the liver may orchestrate the final outcome of the disease. The purpose of this review is to discuss progress in understanding the function of the liver in the early stages of the development of systemic organ dysfunction secondary to acute pancreatitis. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.