Abstract: The aim of this study was to investigate the effect and its possible mechanism of the diterperoid compound 5F isolated from Pteris semipinnata L. on breast cancer growth and metastasis in MDA-MB-231 orthotopic breast tumor xenograft model. The potential side-effects were monitored in addition to its therapeutic effect. RT-PCR and Western blot were applied to detect the expression levels of vascular endothelial growth factor(VEGF), kinase domain insert containing receptor(KDR)in breast cancer tissue. Results showed that 5F significantly suppressed breast cancer growth and metastasis in nude mice by reducing the volume of primate tumor and the number of metastatic nodules in lung. Furthermore, 5F suppressed metastases independent of its inhibitory effect on primary tumor growth. 5F treatment exhibited no toxic effect on liver or kidney in nude mice. 5F can suppress growth and metastasis of MDA-MB-231 breast cancer xenograft. Its mechanism may be involved in the deduction of the expression levels of VEGF and its main receptor KDR in tumor tissue.