Lymphocyte recruitment and activation have been implicated in the progression of cerebral ischemia-reperfusion (I/R) injury, yet the roles of specific lymphocyte subpopulations and cytokines in stroke remain to be clarified. We demonstrated that IL-23 and IL-17, rather than IFN-γ, play pivotal roles in the evolution of brain infarction. IL-23 was produced from infiltrated macrophages in the immediate phase of brain ischemia; thereafter, IL-17-producing T lymphocytes were infiltrated into the ischemic brain tissue in the delayed phase. IL-17 was mostly produced in γδT lymphocytes, and was dependent on IL-23. We discovered that not only IL-23 but also IL-17 deficiency prevented neural cell death in the delayed phase of ischemic brain injury. We also demonstrated that FTY720 administration, which blocked T cell infiltration into the brain, suppressed ischemic brain injury. Furthermore, the depletion of γδT cells also attenuated ischemic brain damages. Therefore, we propose that cerebral T lymphocytes, including γδT lymphocytes, be considered as new therapeutic targets in a novel neuroprotective strategy for ischemic brain injury during the delayed phase.