Abstract: OBJECTIVE To investigate the effect of FTY720 on cognitive function in rats with traumatic brain injury and the related mechanism. METHODS All of 60 male Wistar rats were randomly divided to sham-operation group, model group and treatment group with 20 rats in each group. The rat model of traumatic brain injury was induced by a modification of Feeney’s weight-drop mode1. The Rats were administrated intraperitoneally with 1 mL normal saline or 1 mg·kg^-1 FTY720 respectively before procedures or trauma. A total of 10 rats in each group underwent assessment of cognitive function using localization navigation experiment from Morris water maze and with recorded escape latency. Another 10 rats in each group were killed by decapitation and then their hippocampus tissues were dissected. HE staining was performed to observe morphology of neuronal cells and ELISA was done to determine the concentrations of interleukin-1b, tumor necrosis factor-a and interleukin-6 in brain tissues. RESULTS As compared with sham-operation group, the escape latencies were markedly prolonged (P<0.05), the morphology of neuronal cells in the hippocampus tissues were markedly damaged (P<0.05), as well as the concentrations of interleukin-1b, tumor necrosis factor-a and interleukin-6 in brain tissues were obviously elevated (P<0.05) in model group. compared with model group, the escape latencies were markedly shortened (P<0.05), the morphology of neuronal cells in the hippocampus tissues were markedly recovered(P<0.05), as well as the concentrations of interleukin-1b, tumor necrosis factor-a and interleukin-6 in brain tissues were obviously decreased (P<0.05) in treatment group. CONCLUSION FTY720 can markedly improve the cognitive function of rats with traumatic brain injury and its mechanism may be related to the inhibition of FTY720 on inflammation in central nervous system.