The inhibitory effects of Endostar in combination with radiotherapy in BALB/c nude mice model of human CNE2 nasopharyngeal carcinoma and the mechanism were investigated. In nude mice model of CNE2 nasopharyngeal carcinoma, the inhibitory rate and the sensitizing enhancement ratio (E/O) were calculated according to the tumor volumes in different groups. The expression of microvascular density (MVD) in tumor tissues was examined by using immunohistochemistry staining. The transcription of VEGF gene was detected by using RT-PCR. The inhibitory rate in Endostar+ radiotherapy group was higher than in other groups. In Endostar+ radiotherapy group, the tumor volume was significantly decreased and the E/O ratio was 2.335, suggesting that Endostar could be a radiosensitizer. The expression of MVD of tumor tissues in Endostar+ radiotherapy group was reduced significantly. The expression of the MVD in treatment groups was significantly different from that in control group (P<0.05). Compared to other groups, VEGF mRNA expression in Endostar+ radiotherapy group was decreased remarkably. Endostar in combination with radiotherapy significantly inhibited the growth of CNE2 tumor. The combination therapy decreased the expression of VEGF, and inhibited tumor angiogenesis and proliferation. When combined with radiotherapy, Endostar acted as a radiosensitizer.