Objectives: To explore the correlation between the severity of radiotherapy-induced glossitis (RTG) and endothelial cell injury in local tissues in a rat model. Study Design: The RTG animal model was designed and used by our team. The Oral mucositis index(OMI) was documented daily. Immunohistochemistry (IHC) Staining of CD34 was utilized to identify endothelial cells in the RTG tissues. Apoptosis of endothelial cells in local lesions due to RTG was detected by the TUNEL assay. The dynamic relationship between the OMI and apoptotic endothelial cells was statistically analyzed by time. Results and Conclusions: The injury and apoptosis of endothelial cells were observed 3 day post-irradiation. The vascular lumens of the post-irradiation tongue lesions were irregular; thrombosis formation in the center of the lumens, unsmooth lumen walls and vasodilated vessels were observed. Also, endothelial cells detached from the basal membrane and were found in the lumens. The percentages (%) of apoptotic endothelial cells were 78.3±0.31 (5 day); 89.3±0.83 (8 day); 83.5±0.41 (14 day); 69.3±0.57 (21 day); and 47.3±0.59 (28 day). The OMI was correlated with the percentage of apoptotic endothelial cells (R=0.67, P=0.034). Summary, endothelial cell injury was correlated with the pathogenic condition of RTG. © Medicina Oral S. L.