Abstract: Objective To investigate the change in blood-brain barrier （BBB）permeability and ultrastructure of microvessle in C6 glioma and the tight junction protein expression of claudin-5，which were whole-brain irradiated with 15 Gy，and to explore the time-domain of BBB opened. Methods Sixty tumor-bearing rats (17th day after inoculation) were whole-brain irradiated with 15 Gy,and 10 rats were severally sacrificed at 24 h,3 d,7 d,14 d,21 d and 28 d after irradiation,5 rats were using transmission electron microscopy of exogenous lanthanum nitrate（La3+）-tracing to observe the BBB permeability of the tissues within 2 mm to the border of the tumor and using immunohistochemical method to detect the expression of claudin-5,respectively. Results (1)At 24 h,3 d after exposure,La3+ obviously exuded to the basement membrane（BM）,extra-vascular,the space inside the brain tissue and cells,a little remaining in the endovascular.At 7 d after exposure,La3+ obviously exuded to the basement membrane and brain tissue space less than that in the previous days.At 14d after exposure,La3+ exuded to the local basement membrane.At 21 d,28 d after exposure,La3+ exudation was disappeared.Statistical analysis showed that 24 h,3 d>7 d>14 d>21 d,28 d (P<0.05).(2)claudin-5 expression was mild at 24 h and 3 d after irradiation,showed debris-like expression.claudin-5 expression was light and moderate at 7 d after exposure,combined with deformation and continuous expression.It was moderate expression 14 d after exposure,showed vascular distortion and deformation,but was still continuous state.It was medium-intensity expression at 21 d and 28 d after irradiation,appeared to express both a row and debris.Statistical analysis showed that 24 h,3 d<7 d<14 d<21 d,28 d(P<0.05). Conclusion BBB is opened and gradually resuming 2 weeks after irradiated with 15Gy in C6 glioma which is in time-dependent manner.