Because the mechanism underlying the development of acute pancreatitis (AP) has not yet been fully clarified, it has been a hot but difficult topic in basic and clinical research for a long time. Currently, the dominant hypothesis for the pathogenesis of AP is that it is a disease of self-digestive acute chemical inflammation induced by trypsin activation. As proteins to trigger the inflammatory response cascade, Toll-like receptors (TLRs), especially TLR4, provide a new clue for studying the pathogenesis of AP from the source. Some studies have found that when TLR4 is activated by certain factors, it can amplify an inflammatory effect and aggravate the body's inflammatory response through a series of signal transduction. Toll-like receptor 4 may play an important role in the synthesis and release of proinflammatory cytokines, and the up-regulation of the TLR4 gene may be related with the development and progression of multiple organ injury during AP. As the "gate" of inflammatory response, TLR4 may be closely associated with the development and progression of multiple organ injury during AP. Understanding the roles of TLR4 in AP will help to further clarify the pathogenesis of AP and to search a new target for the treatment of AP.