Background: Microcirculatory disorders play a major part in the pathogenesis of acute pancreatitis. Improvement of microcirculation is hypothesized to open a therapeutic window. The aim of this study was to evaluate the effects of small-volume resuscitation in acute pancreatitis. Methods: In rats, acute pancreatitis of graded severity was induced and pancreatic microcirculation was observed in vivo with an epiluminescent microscope. Primary outcome measures were microcirculation, leukocyte adherence, concentration oftrypsinogen-activating peptide, amylase activity and histopathologic tissue damage. Results: In necrotizing pancreatitis patients receiving prophylactic intervention with 7.5% hypertonic saline the functional capillary density was 76%. Postcapillary venular leukocyte adherence was 45% of vein cross-section. The median histopathologic damage scored 8 points. In controls, a complete microcirculatory breakdown was observed, and in the group with therapeutic intervention no significant difference was detected. In intermediate pancreatitis, the number of perfused capillaries remained 55.0 versus 23.3% in controls. Leukocyte adherence was 40.0 versus 51.7%. The histopathologic damage scored 6.0 versus 9.0 points. Trypsinogen-activating peptide concentration was reduced to 164 versus 402 nM in controls. In cerulein pancreatitis, the number of perfused capillaries was equally preserved in both groups. Conclusion: Small-volume resuscitation preserves capillary microcirculation and prevents pancreatic injury in intermediate necrotizing pancreatitis.