Uncoupling-protein 2 (UCP2) is a mitochondrial protein that appears to be involved in cellular oxidant defense and in the regulation of oncotic cell death, both of which are important features of acute pancreatitis. However, UCP2 expression in acute pancreatitis has not been previously reported. In the current experiments, pancreatic gene expression was studied by real-time reverse-transcription/polymerase chain reaction and Northern blots. Two models of acute experimental pancreatitis were investigated: cerulein-induced pancreatitis in mice at two different time points and taurocholate-induced pancreatitis in rats at two degrees of severity. After cerulein administration, acinar injury and leukocyte infiltration was significantly higher at 24 h compared with 12 h after the first injection of cerulein (P<0.05,>P<0.005, respectively).="" ucp2="" mrna="" was="" unchanged="" at="" 12 h="" but="" was="" nearly="" 12-fold="" greater="" than="" control="" levels="" after="" 24 h="">P<0.001). ucp2="" gene="" expression="" correlated="" with="" acinar="" injury="">r=0.69; P<0.001). by="" 72 h="" after="" taurocholate="" administration,="" the="" severe="" group="" had="" more="" necrosis="" than="" the="" mild="" group="">P<0.005). pancreatic="" ucp2="" mrna="" was="" increased="" fourfold="" in="" the="" severe="" group="" compared="" with="" controls="">P<0.01). ucp2="" expression="" correlated="" with="" parenchymal="" necrosis="">r=0.61; P<0.01). thus,="" pancreatic="" ucp2="" mrna="" increased="" in="" two="" models="" of="" acute="" pancreatitis.="" the="" increase="" in="" ucp2="" gene="" expression="" was="" correlated="" with="" the="" severity="" of="" the="" disease.="" up-regulation="" of="" ucp2="" in="" the="" pancreas="" may="" be="" a="" protective="" response="" to="" oxidative="" stress,="" but="" this="" increase="" may="" also="" have="" a="" negative="" influence="" on="" cellular="" energy="" metabolism.="" therefore,="" acinar="" ucp2="" may="" be="" an="" important="" modifier="" of="" the="" severity="" of="" acute="">