Background and aims: Type IV phosphodiesterase is a key enzyme to metabolize intracellular adenosine 3',5'-cyclic monophosphate (CAMP) expressed in inflammatory cells. The specific type IV phosphodiesterase inhibitor that increases intracellular CAMP is known to be potent suppressor of proinflammatory cytokines. However, the effect of phosphodiesterase inhibitors on the development of pancreatitis has not been well understood. In the present study, we examined the effect of a specific type IV phosphodiesterase inhibitor on experimentally induced pancreatitis. Methods: Severity of cerulein-induced pancreatitis and pancreatic proinflammatory cytokine levels were studied with or without pretreatment with a specific type IV phosphodiesterase inhibitor (rolipram) in Sprague-Dawley rats. Results: Administration of rolipram clearly ameliorated severity of pancreatitis evaluated by edema, serum amylase (P < 0.05), and lipase levels (P < 0.05) in rats. Also, the level of pancreatic proinflammatory cytokine (interleukin-1 beta (IL-1 beta) was significantly reduced when rats were treated with rolipram prior cerulein injection (P < 0.05). Conclusions: Our results demonstrated that intracellular cAMP and pancreatic proinflammatory cytokine level, which are regulated by type IV phosphodiesterase, might play an important role in the pathogenesis of acute pancreatitis. (c) 2006 Elsevier Inc. All rights reserved.