Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced BBB breakdown.Exogenous basic fibroblast growth factor (bFGF) plays essential clues of neuroprotective function in brain injury.The present study therefore investigated the potential beneficial effect of bFGF on BBB after TBI and the underlying mechanisms.In this study, we demonstrated that bFGF reduce neurofunctional deficits and preserve BBB integrity in a mouse model of TBI.bFGF suppressed RhoA and upregulated tight junction proteins, and therefore mitigated BBB breakdown.In vitro, bFGF exerts a protective effect on BBB by upregulating these tight junction proteins claudin-5, occludin, zonula occludens-1, p120-catenin and β-catenin under OGD in HBMECs.Both of these in vivo and in vitro effects are related to the activation of downstream signaling pathway, PI3K/Akt/Rac-1.Inhibition of the PI3K/Akt or Rac-1 by specific inhibitors, LY294002 or si-Rac-1,respectively, partially reduces the protective effect of bFGF on BBB integrity.Overall, our results indicate that the protective role of bFGF on BBB involves the regulation of tight junction proteins and RhoA in the traumatic brain injury model and OGD-induced HBMECs injury, and these effects is underlying the activation of the PI3K/Akt/Rac-1 signal pathway.