The cuprizone mouse model is a well characterized animal model of demyelination. Recently, cortical demyelination has also been observed. Diffusion tensor imaging (DTI) studies have demonstrated the pathology of the corpus callosum (CC) in cuprizone mouse model, but no cortical diffusion changes have been reported. Diffusional Kurtosis Imaging (DKI) quantifies the non-Gaussian behavior of water diffusion, contributing additional information beyond that provided by DTI. Here we report, for the first time, DKI changes in the cortex of mice with demyelination induced by cuprizone, demonstrating the significant advantage of microstructural characterization using DKI, especially for abnormalities in grey matter