Endoplasmic reticulum (ER) is one of the most important cell organelles in the body, regulating protein synthesis, folding and aggregation. Endoplasmic reticulum stress (ERS) is a particular subcellular pathological process involving an imbalance of homeostasis and ER disorder. In the early stage of ERS, cells show a protective unfolded protein response that changes the cellular transcriptional and translational programs to alleviate the process. Therefore, a certain degree of ERS can activate the protective adaptation of cells, whereas sustained severe ERS triggers an apoptotic signal and leads to apoptosis. Acute pancreatitis is a disease caused by trypsin digestion of the pancreas, although the pathogenesis is not completely understood. However, a close association has been suggested between pancreatitis and ERS. This article reviewed relevant research advances and discussed the effect of ERS on the development and progression of acute pancreatitis.