The hTau.P301S-Tg mouse is an excellent model to study human tauopathy but knowledge about how tau affects the microstructure remains limited. We therefore performed anatomical and diffusion MRI to uncover structural regions likely affected by tauopathy and to characterise its progression. No initial morphometrical differences were found at 2.5 months of age. However, at 5 months, hTau.P301S mice exhibited local volumetric cerebellar changes and significantly lower FA and AD values, but higher RD values in inter-cerebellar fibres. Our data indicates that tauopathy results in structural and microstructural changes in the inter-cerebellar fibres, and possibly associates with the model’s motor declines.