Clinically significant depression can impact up to 50% of patients with multiple sclerosis (MS) over a course of their life time, which is associated with an increased morbidity and mortality. In our study, fifteen relapsing-remitting MS (RRMS) patients and 15 age- and gender-matched normal controls were included. Diffusion tensor imaging (DTI) was acquired by employing a single-shot echo planar imaging sequence on a 3.0 T MR scanner and fractional anisotropy (FA) was performed with tract-based spatial statistics (TBSS) approach. Finally, widespread WM and GM abnormalities were observed in RRMS patients. Moreover, the relationships between the depressive symptoms which can be measured by Hamilton depression rating scale (HAMD) as well as clinical disabilities measured by the expanded disability status scale (EDSS) and FA changes were listed. There was a positive relation between EDSS and the FA changes in the right inferior parietal lobule, while negative relation was located in the left anterior cingulate cortex and hippocampus. Also a positive relation between HAMD and FA changes was found in the right posterior middle cingulate gyrus, the right hippocampus, the left hypothalamus, the right precentral gyrus, and the posterior cingulate which demonstrated a link between the depressive symptoms and clinically relevant brain areas in RRMS patients.