Radiation treatment for nasopharyngeal carcinoma (NPC) is common and effective. However, local recurrence occurs frequently. Endostar, a novel recombinant human endostatin, is an antiangiogenic drug with a potent antitumor effect. The present study aimed to observe and explore the radiosensitization effects of Endostar on NPC and its underlying mechanism. The NPC subcutaneous transplantation tumor animal model was established to evaluate the antitumor activity of Endostar combined with radiation (Endostar + radiation) treatment compared with monotherapy (Endostar or radiation). Tumor growth and tumor weight were measured to evaluate the antitumor effect. The level of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were measured using immunohistochemical staining of the tumor tissues. Significant antitumor activity was found in the Endostar + radiation group. The tumor inhibition rates of Endostar, radiation and Endostar + radiation were 27.12, 60.45 and 86.11%, respectively. The VEGF levels in the tumor tissue in the Endostar + radiation group were lower than those in the radiation and control groups. The MVD in the tumor tissues in the Endostar + radiation group was 12.2±2.5, lower than that in the Endostar (29.3±3.4), radiation (23.5±3.6) and control (44.7±5.1) groups. These results suggest that Endostar increases the radiation sensitivity of NPC-transplanted tumors in nude mice by lowering VEGF expression. In this study, the NPC animal model was established, which reflects the efficacy of clinical combination therapies and the combination of Endostar and radiation. The mechanisms of the combination therapies should be further investigated using this model.