The aim of the study was to evaluate the effects of arterial hypotension, high-volume crystalloid resuscitation, and isovolemic hemodilution on pancreatic microvascular perfusion during acute pancreatitis. Using intravital microscopy, pancreatic functional capillary density was analyzed in rats 1 and 2 hr after onset of acute pancreatitis. Pancreatic microvascular perfusion in acute pancreatitis was characterized by a (-62%) significant reduction of functional capillary density predominantly in perinecrotic but also in nonnecrotic tissue (-43%). Pancreatic microvascular perfusion failure was aggravated by arterial hypotension but attenuated by treatment with high-volume crystalloid resuscitation. Isovolemic hemodilution was found superior to high-volume crystalloid resuscitation in maintaining pancreatic functional capillary density and therefore has the best potential in preserving tissue integrity and thereby limiting progression of disease. This study underlines the importance of early fluid resuscitation/hemodilution in patients presenting with acute pancreatitis.