Aim To investigate the mechanism of cerebral infarction on regulating microglias M1/M2 phenotypic transformation by retinoid acid receptorrelated orphan receptor α(RORα). Methods (1) Directionally transform microglias into the M1 state and the M2 state, the expression of RORα, M1 marker inducible nitric oxide synthase (iNOS) and M2 marker arginase-1 (Arg-1) were deteced by Western blot. (2) Middle cerebral artery embolism (MCAO) model were established, the protein expression of RORα, iNOS, Arg-1 in brain tissues were detected by Western blot after ischemic brain injury at different time points (6 h, 24 h, 3 d and 7 d). (3) RORα-siRNA was injected intracerebroventricularly of mice and MCAO model were established 72 h later, brain function was evaluated by neurobehavioral score (Longa score), the protein expressions of iNOS, Arg-1 and RORα in brain tissues were detected by Western blot. (4) RORα-overexpressed lentivirus was injected intracerebroventricularly of mice, MCAO model were established 7 d later, brain function was evaluated by neurobehavioral score (Longa score), the protein expressions of iNOS, Arg-1 in brain tissues were detected by Western blot. Results Microglias can transform to M1 state induced by LPS/IFN-γ and transform to M2 state induced by IL-4/IL-13. Compared with the control group, RORα expression was significantly increased in M2 state microglias and significantly decreased in M1 state microglias (P<0.01). After cerebral ischemia reperfusion, compared with the Sham group, protein expression of iNOS were significantly increased and peaked in 6 h, then gradually decreased, protein expression of Arg-1 gradually increased in 3 d and 7 d, protein expression of RORα were increased and peaked in 3 d, then significantly decreased in 7 d, the results suggested that M1 state microglias were dominant in cerebral ischemia injury early stage, and M2 state microglias were dominant in cerebral ischemia injury late stage, RORα was highly expressed in the medium stage of cerebral ischemia reperfusion. After down-regulation of RORα expression, the neurobehavioral score was significantly increased, brain function were injured seriously, the protein expression of Arg-1, RORα were significantly decreased and the protein expression of iNOS were significantly increased in MCAO group. After up-regulation of RORα expression, the neurobehavioral score of MCAO group were decreased significantly, the brain function injury was improved. The protein expression of Arg-1 were significantly increased and the protein expression of iNOS were significantly decreased in MCAO group. Conclusion RORα was involved in brain injury after cerebral infarction by regulating the transformation of microglias from M2 state to M1 state.