Traumatic brain injury (TBI) is a disease burden worldwide and it is associated with axonal injury and neuroinflammation. Investigating the underlying mechanisms and the progression in the acute and sub-acute stages following TBI non-invasively would aid for early diagnosis and intervention. In this study, we used diffusion tensor imaging (DTI) to investigate the microstructural changes following TBI. Furthermore, we used immunohistochemistry to investigate the axonal injury and microglial activity following TBI. Using DTI, we detected persistent microglial activity associated with TBI which might suggest a possible use of DTI for reflecting on the microstructural changes associated with TBI in humans.