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AIM: To elucidate the role of COX-2 in the development of capillary leakage in rats with acute interstitial pancreatitis.METHODS: Rats with acute interstitial pancreatitis were induced by caerulein subcutaneous injection. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of COX-2 in pancreatic tissues, spectrophotometry was used to assay the parameters of acute pancreatitis such as the serum amylase and plasma myeloperoxidase, and determination of capillary permeability in the pancreas by quantifying the permeability index (PI) assisted response of pancreatic microvascular via intravital fluorescence microscope video image analysis system.RESULTS: A significant increase of COX-2 expression,elevation of serum amylase, and plasma myeloperoxidase were detected in rats with acute edematous pancreatitis compared with control rats. The changes of pancreatic microvascular after caerulein injection were as following: (a) the decrease of pancreatic capillary blood flow (4th h,0.56±0.09 nL/min, P＜0.05; 8 th h, 0.34±0.10 nL/min, P＜0.001);(b) reduction of functional capillary density (4 th h, 381±9 cm-1,P＞0.05; 8th h, 277±13 cm-1 P＜0.001); (c) irregular and intermittent capillary perfusion was observed at the 8th h and these vessels were also prone to permeation.CONCLUSION: COX-2 plays an important role in mediating capillary permeability in pancreatitis, thereby contributing to capillary leakage.