Objective: This exploratory study examines whether interictal plasma pituitary adenylate cyclase-activating peptide 38-like immunoreactivity shows correlation with the microstructural integrity of the white matter in migraine. Methods: Interictal plasma pituitary adenylate cyclase-activating peptide 38-like immunoreactivity was measured by radioimmunoassay in 26 migraine patients (24 females) who underwent diffusion tensor imaging (DTI) afterwards using a 1.5T MR scanner. Data were analysed using Tract-based Spatial Statistics (TBSS) included in FMRIB’s Software Library (FSL). Results: Interictal plasma pituitary adenylate cyclase-activating peptide 38-like immunoreactivity showed significant correlation with mean diffusivity (p<0.0179) mostly in the bilateral occipital white matter spreading into parietal and temporal white matter. Axial and radial diffusivity showed positive correlation with interictal pituitary adenylate cyclase.activating peptide 38-like immunoreactivity (p<0.0432 and p<0.0418, respectively) in the left optic radiation and left posterior corpus callosum. Fractional anisotropy did not correlate significantly with pituitary adenylate cyclase-activating peptide 38-like immunoreactivity. With disease duration as a nuisance regressor in the model, pituitary adenylate cyclase-activating peptide 38-like immunoreactivity correlated with axial and mean diffusivity in the left thalamus (p<0.01). Conclusion: We report a link between pituitary adenylate cyclase-activating peptide 38, a pathobiologically important neurochemical biomarker, and imaging markers of the disease that may bolster further research into the role of pituitary adenylate cyclase-activating peptide 38 in migraine.