This review article analyzes, through a nonsystematic approach, the pathophysiology of acute pancreatitis (AP) with a focus on the effects of thoracic epidural analgesia (TEA) on the disease. The benefit-risk balance is also discussed. AP has an overall mortality of 1 %, increasing to 30 % in its severe form. The systemic inflammation induces a strong activation of the sympathetic system, with a decrease in the blood flow supply to the gastrointestinal system that can lead to the development of pancreatic necrosis. The current treatment for severe AP is symptomatic and tries to correct the systemic inflammatory response syndrome or the multiorgan dysfunction. Besides the removal of gallstones in biliary pancreatitis, no satisfactory causal treatment exists. TEA is widely used, mainly for its analgesic effect. TEA also induces a targeted sympathectomy in the anesthetized region, which results in splanchnic vasodilatation and an improvement in local microcirculation. Increasing evidence shows benefits of TEA in animal AP: improved splanchnic and pancreatic perfusion, improved pancreatic microcirculation, reduced liver damage, and significantly reduced mortality. Until now, only few clinical studies have been performed on the use of TEA during AP with few available data regarding the effect of TEA on the splanchnic perfusion. Increasing evidence suggests that TEA is a safe procedure and could appear as a new treatment approach for human AP, based on the significant benefits observed in animal studies and safety of use for human. Further clinical studies are required to confirm the clinical benefits observed in animal studies.