A moderate focal contusion injury model in swine was used to evaluate treatment response to cyclosporine, a neuroprotective agent, using diffusion tensor imaging. This work builds upon the recent work in which we demonstrated improved neurological outcomes after administration of cyclosporine in the acute time period following traumatic brain injury (TBI). Regions of interests were drawn on the peri-contusion regions. We observed significant elevations in FA and CL and significant decline in CS from cyclosporine groups compared to those of placebo. These findings suggest that DTI may be useful in assessing treatment response to cyclosporine in a porcine model of TBI.