Objective In patients with painful chronic pancreatitis (CP) there is increasing evidence of abnormal pain processing in the central nervous system. Using magnetic resonance (MR) diffusion tensor imaging, brain microstructure in areas involved in processing of visceral pain was characterised and these findings were correlated to clinical pain scores. Methods 23 patients with CP pain and 14 controls were studied in a 3T MR scanner. Apparent diffusion coefficient (ADC) (ie, diffusivity of water) and fractional anisotropy (FA) (ie, organisation of fibres) values were assessed in the amygdala, cingulate cortex, insula, prefrontal cortex and secondary sensory cortex. Daily pain scores and the Brief Pain Inventory Short Form were collected 1 week before the investigation. Results In grey matter, patients had increased ADC values in amygdala, cingulate cortex, insula and prefrontal cortex, as well as decreased FA values in cingulate cortex and secondary sensory cortex. In white matter, patients had increased ADC values in insula and prefrontal cortex, and decreased FA values in insula and prefrontal cortex (all p values 0.05). Microstructural changes in cingulate and prefrontal cortices were correlated to patients' clinical pain scores. Conclusion The findings suggest that microstructural changes of the brain accompany pain in CP. The changes are likely to be a consequence of ongoing pain and structural reorganisation of the neuromatrix as also seen in other diseases characterised by chronic pain.