Postpartum depression (PPD), a main cause of maternal suicide, is an important issue in perinatal mental health. Recently, cerebral diffusion tensor imaging (DTI) studies have shown reduced fractional anisotropy (FA) in major depressive disorder (MDD) patients. There are, however, no reports using diffusion kurtosis imaging (DKI) for evaluation of PPD. This was a Japanese single-institutional prospective study from 2016 to 2019 to examine the pathophysiological changes in the brain of PPD patients using DKI. The DKI data from 3.0 T MRI of patients one month after delivery were analyzed; the patients were examined for PPD by a psychiatrist. The mean kurtosis (MK), FA and mean diffusivity (MD) were calculated from the DKI data and compared between PPD and non-PPD groups using tract-based spatial statistics analysis. Of the 75 patients analyzed, eight patients (10.7%) were diagnosed as having PPD. In the PPD group, FA values in the white matter and thalamus were significantly lower and MD values in the white matter and putamen were significantly higher. The area with significant differences in MD value was more extensive (40.8%) than the area with significant differences in FA value (6.5%). These findings may reflect pathophysiological differences of PPD compared with MDD.