This study aims to use a two-compartment diffusion model of white matter based on diffusional kurtosis imaging (DKI) to explore early white matter alternations in middle-aged type 2 diabetes mellitus (T2DM) . 33 T2DM patients and 13 healthy control were enrolled. All diffusion parameters (FA=fractional anisotropy, MD=mean diffusivity, AD=axial diffusivity, RD=radial diffusivity, MK=mean kurtosis, AK=axial kurtosis, RK=radial kurtosis, Da=intra-axonal diffusivity, De∥=axial extra-axonal space diffusivity, De⊥= radial extra-axonal space diffusivity) were compared. De⊥ was demonstrated to be the most sensitive in detecting the diffusion changes. These increased De⊥ (extra-axonal diffusivity) and unchanged Da (intra-axonal diffusivity) reflected the increased water and/or demyelination.