Aims: To compare the immunogenicity and anti-tumor effects of gene vaccines encoding domains 1-4 with full length of extracellular region of VEGFR2. Results: Both DNA vaccines decreased VEGF levels and rose specific antibodies; the lymphocyte subsets of vaccinated mice maintained high; tumor latency period and survival time of immunized mice were prolonged; tumor size, weight, MVD and liver metastases were significantly less than the control groups. Methods: Mouse model of CT-26 adenocarcinoma of colon were treated with orally immunized gene vaccine encoding extracellular 1-4 and full length of VEGFR2 respectively. The effect of anti-tumor was evaluated by detecting the tumor volume, mice survival time, intratumoral microvessel density (MVD) and liver metastases. To explore the reasonable mechanism of the oral gene vaccines, the levels of VEGF and anti-VEGFR2 antibody in serum were detected by ELISA, CD4(+) and CD8(+) T cells in peripheral blood and subcutaneous tumors were analyzed by flow cytometer and immunohischemistry respectively. Conclusion: Compared with full length of extracellular domain of VEGFR2, extracellular regions 1-4 of VEGFR2 has been sufficient to decrease the serum VEGF level and to inhibit tumor growth and metastasis specifically.