The different effects of cyclosporine and rapamycin on tumor progress and metastasis and their mechanisms were investigated. BTT-T739-gfp cell line stably expressed green fluorescence protein was intracutaneously inoculated into 24 mice. One week later, the mice were randomly divided into 3 groups and treated intraperitoneally by normal saline (as control), cyclosporine and rapamycin respectively. Survival rate and tumor volume were measured. The tumor metastasis, pathological angiogenesis and expression of angiogenesis-associated genes were analyzed. The metastasis analysis in lung and liver were also accomplished under the fluorescent microscope. Compared with the normal saline and cyclosporine, the general immunosuppressive dosage of rapamycin effectively inhibited the progress and metastasis of the established tumors. It was the rapamycin that improved the survival rate of tumor-beared mice and decreased the developmental velocity of tumor volume, to which was significantly different from the control and cyclosporine groups on the 12th day and 14th day. Experimentally, rapamycin inhibited tumor growth through angiogenesis and metastases repression in the established mouse model. From a mechanistic perspective, rapamycin showed anti-angiogenetic activities related to decrease of VEGF-A production which was a result of the down-regulation on the transcriptional level of VEGF-A and its transcription activator HIF-1α. It implied that conventional immunosuppressants showed different therapeutic roles on established tumors. Rapamycin, not cyclosporine could inhibit the tumor growth and metastasis of which was referred to anti-angiogenesis.