Blast induced traumatic brain injury (bTBI) is a serious concern for military personnel exposed to primary blast. Computational models and imaging diagnostics are useful tools that are commonly used to study mechanical response of the brain during trauma, but rely on information about the mechanical property changes due to injury. In this study, thirty adult, male Sprague-Dawley rats were exposed to varying levels of primary blast which were generated using a compressed-gas driven shock tube. Animals were sacrificed at 2 and 24hrs following trauma and their brain tissue immediately removed for post trauma, tissue-level stiffness assessment using a mechanical indenter. Ramp and hold indentation tests with a cylindrical indenter were performed to measure the mechanical response of the tissue. Significantly higher forces were measured in the midbrain inferior region in the blast high 24 hour when compared to sham group (+57.7%, p=0.02). In addition, we observed lower forces in the brainstem region (-65%, p=0.04) of the blast low 24 hour as compared to the sham group. There were no significant changes in the 2 hour groups. The results show a temporal, regionally-dependent, and severity-dependent mechanical response;​—stiffening in the blast high 24 hour, softening in blast low 24 hour—to injury. These results provide insight to the effect of bTBI on the mechanical response of brain tissue, which may help improve computational models of the head and imaging diagnostics focused on detecting bTBI.