〔Abstract〕 Objective To observe the expression and trends of tight junction proteins Occludin and zonula occluden-1(ZO-1) in blood-brain barrier(BBB) of rats with traumatic brain injury(TBI), and to explore the intervention effect of cannabidiol(CBD) on the BBB. Methods The TBI model of rat was prepared by modified “Feeney free fall method” and randomly divided into three groups: the sham-operated group(Sham group), the model group(TBI+vehicle group) and the CBD intervention group(TBI+CBD group), with 24 rats in each group. Each group was subdivided into six time points: 8 h, 1, 2, 3, 5 and 7 d after injury. The expression of Occludin and ZO-1, which are closely related to the permeability of BBB, was detected by immunohistochemistry, immunofluorescence staining and Western blot at different points. The permeability of BBB was detected by sodium fluorescein assay. Results The results of immunohistochemistry showed that compared with Sham group, the positive expression of Occludin and ZO-1 decreased with time after brain trauma(P<0.05), and both reached the lowest level at 2 d. The expression levels of Occludin and ZO-1 were up-regulated after 1 d of CBD intervention(P<0.05). Immunofluorescence staining showed a similar trend to Western blot results, with Occludin and ZO-1 fluorescence expression intensity and protein expression reduced after TBI compared with Sham group(P<0.05). And the expression levels of Occludin and ZO-1 were up-regulated after 2 d of CBD intervention(P<0.05). The results of fluorescein sodium experiment showed that the BBB integrity of brain tissue was destroyed after TBI, and the permeability increased after TBI(P<0.01). The permeability of BBB decreased after CBD intervention(P<0.05). Conclusion The expression of tight junction proteins Occludin and ZO-1 decreases after TBI, and the permeability of BBB is disrupted, and CBD intervention reverses the disruption of the BBB by TBI.