Inflammatory effects contribute to the pathogenesis of pancreatitis. Clearly, pro-inflammatory cytokines like TNF- and IL-6 are involved in this process and the associated systemic complications. The MAPKAPK-2 (MK2) signalling pathway is involved in cytokine gene-expression. Therefore, we hypothesized that blockade of this pathway inhibits the expression of pro-inflammatory cytokines and thereby protects against pancreatitis. To investigate this, we used an in vivo mouse model with a homozygous deletion of the MK2 gene. Pancreatitis was induced by injection of cerulein. The severity was determined by measuring serum lipase, pancreatic trypsin activation, pancreatic edema and morphologic changes by quantitative scoring of histologic sections. Systemic inflammation was evaluated by measuring myeloperoxidase activity in lung tissue. Serum levels of TNF- and Il-6 were measured using an ELISA, mRNA levels were identified using RT PCR and subsequent quantitative PCR analysis. Pancreatitis in animals with deletion of the MK2 gene is less severe and accompanied with reduced serum levels of TNF- and IL-6. Pancreatic mRNA levels revealed a 4-fold reduction of IL-6 mRNA expression in MK2 -/- mice. Effects were associated with suppression of pancreatic trypsin activity and reduced acinar cell injury. In summary, these data show that gene deletion of MK2 ameliorates cerulein-induced pancreatitis. TNF- and IL-6 signalling is mediated by the MK2 pathway and therefore crucial for the regulatory inflammatory processes. TNF- expression is supposable regulated by a post-transcriptional mechanism, whereas IL-6 expression is most likely regulated by transcriptional effects.