Acute pancreatitis is an autodigestive and inflammatory process, frequently associated with the systemic inflammatory response syndrome (SIRS) and organ failure. This is of major importance because half of deaths in the first weeks of the process are attributed to organ failure. Several proinflammatory mediators have been identified to play a role in the progression of the local pancreatic damage to the systemic inflammation. Since macrophages orchestrate both the initiation and resolution of inflammation, it could be suspected that the degree of systemic macrophage activation could be one of the factors that finally determine the severity of the process. Factors that determine the activation of macrophages includes cytokines released by pancreatic acinar cells, free radicals generated by different biological processes as well as mediators produced by pancreatic enzymes released during the progression of the disease. However, in addition to the direct pro-inflammatory activity, there are also other effects that negatively regulate the expression of pro-inflammatory genes and play a role in the resolution of the inflammatory processes. In this sense, lipolytic enzymes released by pancreas plays a role in the fat necrosis observed in the severe forms o the disease and generate different lipidic mediators that interfere the normal regulation of macrophage activation trough the interaction with nuclear factors as PPARg. These interferences could determine the intensity of macrophage activation and the final evolution of the disease.