Objective：To verify genistein’s anti-angiogenic effect on MKN 45 gastric cancer cells and its subcutaneous xeno-transplanted tumors and to develop an optical imaging method for monitoring this anti-angiogenesis. Methods：MTT assay and VEGF-ELISA were performed to test the inhibitory effect of genistein on proliferation of MKN45 human gastric cancer cells and VEGF expression. IHC was applied to detect VEGF，CD31 and Ki67 expression after MKN45 subcutaneous xeno-transplanted tumors being treated with genistein. The optical molecular probe targeting VEGF：Dylight 680-Bevacizumab-F（ab′）2 was firstly prepared by conjugating near-infrared fluorescent dye Dylight 680-NHS and bevacizumab’s F（ab′）2 fragments. Then，it was applied in in vivo optical imaging to verify tumor VEGF down regulation induced by genistein. Results：Results of MTT（P=0.118） and Ki67 IHC showed that genistein had no significant inhibitory effect on the proliferation of MKN45 human gastric cancer cells and its subcutaneous xeno-trans-planted tumors. VEGF-ELISA results showed geni-stein could significantly down regulate VEGF expression of MKN45 cells and its xeno-transplanted tumors（P=0.000）. Re-sults of genistein treatment indicated that genistein had a certain anti-tumor effect（P=0.034）. IHC results showed tumor VEGF and CD31 expressions were both reduced after genistein treat－ment. In addition，Dylight 680-Bevacizumab-F（ab′）2 applied to in vivo optical imaging could effectively detect reduced VEGF ex－pression. Conclusion：The inhibitory effect of genistein is mainly realized by genistein’s anti-angiogenesis，which significantly inhibit tumor VEGF expression，rather than genistein’s direct tumor proliferation inhibition. Optical molecular probes Dylight 680-Beva－cizumab-F（ab′）2 applied in vivo optical imaging，with favorable clinical prospect，could predict anti-angiogenic effect of genistein at early stage.