Abstract： Objective To investigate the changes and the molecular mechanism of tight junctions of blood-brain barrier (BBB) in human glioma. Methods A retrospective analysis was conducted in 21 patients with glioma of different grades and 6 healthy adults and thus we divided them into normal tissue group (n=6), low-grade glioma group (n=11) and high-grade glioma group (n=10).Each group was sampled for ultrastructural observation of the tight junctions of BBB using transmission electron microscope. Double immunofluorescence staining and RT-PCR were used to observe andanalyze the protein and mRNA expressions of Claudin-5 in the glioma, respectively. Results In normal brain tissues, the para-cellular cleft between the adjacent endothelial cells was sealed by continuous strands of tight junctions. In low-grade glioma, most of the tight junctions were intact and no fenestration was found in the endothelium. In high-grade glioma, the amount of pinocytosis vesicle was increased and significant paracellular cleft was found between the adjacent endothelial cells; in addition,typical fenestrations were found in the endothelial cells. Double immunofluorescence staining showedstrong expression of Claudin-5 in the microvascular endothelial cells in the normal brain tissues but weakexpression of that in the high-grade glioma. In the low-grade glioma, expression of Claudin-5 wasdecreased slightly in the microvascular endothelial cells. Compared with the high-grade glioma, the low-grade glioma and normal brain tissues showed significantly higher mRNA expression level of Claudin-5 (P<0.05). Conclusion In the development of brain glioma, glioma cells can decrease the expressions of Claudin-5 and interrupt the continuity of the tight junctions in BBB; and the decrease of Claudin-5 may be one of the important molecular mechanisms explaining the paracellular cleft of tight junction in BBB.