Background: Chronic relapsing inflammatory optic neuropathy (CRION) is an inflammatory optic neuropathy, characterized by relapses and remissions in patients with normal brain and spinal magnetic resonance imaging (MRI). Discrepancy from other demyelinating diseases is important, and it is still uncertain whether CRION is restricted to the optic pathways or it affects other brain white matter (WM) structures. Objective: To assess WM structure in patients with CRION by using diffusion tensor imaging (DTI). Methods: DTI was performed in six CRION patients and six age-and sex-matched healthy controls on a 3 T scanner. Tract-based spatial statistics (TBSS) was used for voxelwise statistical analysis of DTI data. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) measures were obtained. Results: TBSS analysis revealed two different patterns of WM alterations in patients with CRION. The optic chiasm and connected structures had significantly higher FA and lower RD, AD and MD in the patients than in the healthy controls. On the other hand, anterior frontal bundles of inferior fronto-occipital tracts, left uncinate fascicule and internal capsule showed decreased FA and increased RD. No correlation was found between the clinical variables and diffusion measures. Conclusion: WM appearing normal on brain MRI shows widespread abnormalities in a cohort of CRION patients as assessed by DTI.