Aim of the study was to investigate pancreatic microcirculatory and histopathological changes in rats after chronic ethanol liquid diet feeding.To investigate the influence of chronic alcohol exposition (CAE) on the pancreas, rats were fed with either Lieber-DeCarli (LDC) control diet or LDC alcohol diet for 2, 4, or 6 weeks and received additionally an acute ethanol administration (AEA) for 90 minutes. Intravital microscopy was performed at baseline, 45 minutes, and 90 minutes after starting AEA. Pancreatic perfusion and leukocyte adhesion were assessed, and pancreatic damage was evaluated by histology.Capillary perfusion was reduced in all animals after AEA. After previous CAE, there was a significant increase in leukocyte adhesion compared to control groups (P < 0.05). Most importantly, leukocyte adhesions were already increased at baseline after CAE and before the acute bolus was infused (P < 0.05). Moreover, only animals that received LDC alcohol diet developed mild histological changes consisting of pancreatic edema and vacuoles, whereas those that received AEA alone did not. Histological changes and cytokine levels correlated with the duration of prior CAE.Long-term alcohol intake activates endothelium and sensitizes the pancreas for inflammatory reactions leading to an increased likelihood of a clinically evident episode of acute pancreatitis.