Objective:The purpose of this study was to investigate the effect of an angiogenesis inhibitor (TNP-470) on the ultra micro- structural morphological changes of GNM cell line, which was derived from human oral squamous cell carcinomas in vitro.Meth- ods:The GNM cells were cultured and, the effect of TNP-470 on ultra micro-structural morphological changes of GNM cells was observed under the inverted microscope, the scanning electron microscope (SEM) and the transmission electron microscope (TEM).Results:Numerous round cells, shrinkage of cellular membrane and dead cells were observed 48 hours after 2Lg/ml of TNP-470 was added into the GNMcellular suspension. After72 hours, GNMcells became shortened and, the numberofmicrovilli of the cellular surface was observed under the SEM and TEM. A large number of GNM cells turned into necrosis, accompanying with the destruction of mitochondria and endoplasmic reticula.Conclusion:TNP-470 has a strong tumor cytotoxic effect on GNM cells, which may be due to its destructibility on mitochondria and endoplasmic reticula of GNM cells. TNP-470 can alter the sur- face structure of GNM cell membrane, which suggests that TNP-470 may interrupt the metastasis of GNM cells.