Our purpose was to investigate brain-derived neurotrophic factor (BDNF) in chronic pancreatitis (CP) in comparison with the normal pancreas and to evaluate its association with pain. By immunohistochemistry, in the normal pancreas BDNF immunoreactivity was moderately present in the cytoplasm of most ductal cells and weakly present in most acinar cells, islet cells, nerve fibers (including perineurium), and ganglia cells. In contrast, in CP intense immunostaining of BDNF was present in most cells of ductular complexes and in the perineurium of enlarged nerves. Moderate immunostaining of BDNF was found in degenerating acinar cells and islet cells. In addition, moderate immunoreactivity of BDNF was also detected in most enlarged nerve fibers and intrinsic pancreatic ganglia cells in CP samples. Western blot analysis also revealed 5.6-fold higher BDNF levels in CP samples (P < 0.01) compared with normal pancreas samples. The expression level of BDNF was positively correlated with pain intensity (P < 0.01) and pain frequency (P < 0.01) of CP patients. Furthermore, there was a significant relationship (r = 0.68, P < 0.01) between the BDNF immunostaining and the global pain scores. BDNF is increased in CP. Its association with pain suggests that it functions as a peripheral and central pain modulator, as reported previously in other inflammatory disorders.