Objective To study the histopathological changes and ultrastructure features of human gliomas after receiving stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT), and observe the changes of tumor-associated factor Ki-67 level, endothelial growth factor (VEGF) level and microvessel density (MVD).Methods A comparative, retrospective study of pathological and immunohistochemical changes of 25 gliorna specimens without radiotherapy (controls) and 25 patients with glioma received with SRS and SRT (treatment group), admitted to our hospital from November 1995to July 2008, were carried out. Eight specimens from both groups, fixed with glutaraldehyde, were chosen for electron microscope observation; the ultrastructure changes in the tumor center, tumor margin and peripheral edema brain tissues in each specimen were observed. Immunohistochemical staining was employed to detect the expressions of Ki-67 and VEGF, and the MVD. And these data were statistically analyzed. Results The square and extent of tumor necrosis and liquation were positively significantly correlated with the tumor grade (r=0.649, P=0.001). Electron microscope indicated that the organdles,capillaries and blood-brain barrier in the tumor center, tumor margin and peritumoral edema cortex of the treatment group occurred different degrees of brain tissue degeneration and necrosis; while these were without damage in the controls. Immunohistochemistry showed that the protein expression of VEGF, the Ki-67 positive cells, and the MVD in the control group and treatment group were positively correlated with the glioma grade (P＜0.05). Of the glioma with the same grade, the Ki-67 protein expression and MVD in the treatment group were significantly lower than those in the control group (P＜0.05).Conclusion SRS and SRT may lead tumor cells to different degrees of degeneration, necrosis, and apoptosis, as well as the three-tier structure damage of capillaries in the blood-brain barrier, which provides a laboratory and theoretical foundation to take individualized comprehensive treatment of different gliomas.