In the present study we analyzed the three phospholipase A2 isoforms phospholipase A2 type I (PLA2-I), phospholipase A2 type II (PLA2-II), phospholipase A2 type IV (PLA2-IV) in chronic pancreatitis in comparison with normal pancreas. PLA2-I also named pancreatic phospholipase is a digestive enzyme while PLA2-II and PLA2-IV play an important function in inflammatory reactions. In chronic pancreatitis PLA2-I mRNA expression was significantly reduced. In contrast, PLA2-II and PLA2-IV mRNA were increased in 73% of the chronic pancreatitis samples (PLA2-II; 5.7-fold overexpressed; PLA2-IV:5.1-fold overexpressed; p < 0.05). By in situ hybridization the highest expression signals were found in chronic pancreatitis samples in areas with ductal metaplasia. Immunohistochemistry of PLA2-II revealed also the strongest immunoreactivity in ductal metaplasia. Increased PLA2-II and PLA2-IV mRNA levels were associated with a higher degree of tissue destruction, ductal metaplasia and degree of fibrosis. Our findings indicate that PLA2-II and PLA2-IV seems to play a role in the pathobiological alterations in chronic pancreatitis and contribute to the morphological changes which occur in chronic pancreatitis.