Angiogenesis is an essential process for the growth and invasion of cancer. However, it is uncertain that anti-angiogenic effects can be a major treatment strategy of oral cancer. The aim of this study was to investigate whether thalidomide and paclitaxel, which are known to be potent inhibitors of angiogenesis, have inhibitory effects on the growth of oral squamous cell carcinoma (OSCC) xenotransplanted into nude mice and whether anti-angiogenesis can be included as a major treatment strategy of oral cancer. After human OSCC cell line, KB, was subcutaneously inoculated into 32 nude mice, the volume of tumor was measured every 3 days. When the tumor mass reached 300-500 mm3, thalidomide (200 mg/kg) and paclitaxel (13 mg/kg) were administered into the animals and tumor volume change was checked. The excised tumor masses on the 30th day after administration were frozen and processed for immunohistochemistry using vascular endothelial growth factor (VEGF) and CD31, and for real-time reverse transcription-polymerase chain reaction (RT-PCR). We evaluated VEGF expression and the expression of its mRNA and CD31 for vessel density. Paclitaxel showed an inhibitory effect on the growth of transplanted human OSCC and reduced the immunohistochemical expression of VEGF and CD31 and VEGF mRNA (P<0.01). Thalidomide also lowered remarkably VEGF expression (P<0.01) and CD31 (P<0.01) as well as VEGF mRNA (P<0.05), but it did not show statistically significant inhibitory effect on the tumor growth. These results suggest that the growth of human OSCC is not simply dependent on VEGF-induced angiogenesis and that anti-angiogenic therapy alone is not likely to be effective for the treatment of OSCC, but might be regarded as adjuvant chemotherapeutic strategy.