The Notch signaling pathway is an important pathway in the adult pancreas and in pancreatic ductal adenocarcinoma (PDAC), with HES1 as the core molecule in this pathway. However, the roles of HES1 in the adult pancreas and PDAC formation remain controversial. Methods: We used genetically engineered dual-recombinase mouse models for inducing Hes1 deletion under various conditions. Results: The loss of Hes1 expression in the adult pancreas did not induce phenotypic alterations. However, regeneration was impaired after caerulein-induced acute pancreatitis.