Objective To observe the effect of tacrolimus on neurological outcomes after traumatic brain injury (TBI) in rats through the activation of nuclear factor of activated T cell c1 (NFATc1).Methods The fluid percussion injury model of TBI was used in the study.Ninety SD rats were divided into Sham group,TBI group and Tacrolimus group according to the random number table.Sham group received intraperitoneal saline solution injection for 7 days after sham injury.TBI group and Tacrolimus group were respectively administered intraperitoneal saline solution injection or tacrolimus (1 mg/kg) for 7 days after the induction of FPI.Severity of neurological dysfunction effects was evaluated using the modified neurological severity score (mNSS) and level of aquaporin 4 (AQP4) mRNA.Levels of interleukin-2 (IL-2) and interferon-γ (IFN-γ) protein and mRNA were detected by RT-PCR and ELISA method.Activation of CaN/NFATc1 signal was checked by RT-PCR,Western blot and immunofluorescence staining.Results mNSS in Tacrolimus group was significantly reduced compared to TBI group at days 1,7 and 14 postinjury (P ＜0.05),but the score remained higher than that in Sham group.Expression of AQP4 mRNA in Tacrolimus group was significantly reduced compared to TBI group at day 1 postinjury,but the level remained higher than that in sham group.Expressions of IL-2 and IFN-γmRNA and protein in tacrolimus group were reduced compared to TBI group,especially at day 1 postinjury (P ＜ 0.05).Expressions of CaN mRNA and protein in tacrolimus group were significantly down-regulated compared to TBI group (P ＜0.05).NFATc1 nuclear entry was obvious at day 7 postinjury,but tacrolimus displayed an inhibitory effect against the nuclear entry of NFATc1 (P ＜ 0.05).Conclusion Tacrolimus relieves inflammatory responses,attenuates brain edema after moderate TBI and facilitates neurological outcomes by regulating the NFATc1.