Although the pancreatic heat shock response has already been reported to confer protective effects during experimental pancreatitis, the mechanism of action remains unknown. We investigated the effects of hyperthermia in cerulein-induced pancreatitis. Heat shock protein 70 (HSP70) expression in rats was induced by a 20-min period of water immersion (42°C). The severity of pancreatitis as well as the pancreatic expression of cytokines, nuclear factor-B (NF-B), and inhibitory factor B- (IB-) were evaluated in the presence and absence of hyperthermia. We found that hyperthermia resulted in time-dependent expression of HSP70 within the pancreas associated with a reduction in the severity of acute pancreatitis. Tumor necrosis factor- and intercellular adhesion molecule-1 expression was significantly reduced in the presence of hyperthermia. Moreover, NF-B activity was delayed in the presence of hyperthermia whereas IB- was stabilized in the cytoplasm. These results suggest that hyperthermia decreases the severity of cerulein-induced pancreatitis by decreasing cytokine expression in the pancreas through the modulation of NF-B activity.