Mild blast-induced traumatic brain injury (mbTBI) poses special diagnostic challenges due to its overlapping symptomatology with other neuropsychiatric conditions and the lack of objective outcome measures. Diffusion tensor imaging (DTI) can potentially provide clinically relevant information toward a differential diagnosis. In this study, we aimed to determine if single and repeated (5 total; administered on consecutive days) mild blast overpressure exposure results in detectable structural changes in the brain, especially in the hippocampus. Fixed rat brains were analyzed by ex vivo DTI at 2 h and 42 days after blast (or sham) exposure(s). An anatomy-based region of interest analysis revealed significant interactions in axial and radial diffusivity in a number of subcortical structures at 2 h only. Differences between single- and multiple-injured rats were largely in the thalamus but not the hippocampus. Our findings demonstrate the value and the limitations of DTI in providing a better understanding of mbTBI pathobiology.