Angiogenesis plays an important role in tumor development. We have previously demonstrated the antiangiogenic effect of Kint3-4 and leucurogin, two recombinant proteins, which when administered at 5 µg/day, reduced the weight and volume of solid Ehrlich and melanoma tumors implanted in mice. In this work we demonstrate the synergistic effect of these proteins. Swiss mice were inoculated with Ehrlich tumor and after seven days the treatment with the proteins administered individually (Kint3-4 or leucurogin), or with associated proteins (AP), Kint3-4 and leucurogin, was initiated with daily doses of 5 or 10 µg of the proteins. On the eighth day the animals were anesthetized and the perfusion image of the tumor region was generated by laser Doppler. Blood flow was observed to be reduced by 25 to 29% in the tumor of animals after individual treatment (IT) with 10 µg of proteins while treatment with 10 µg of associated proteins reduced the blood flow by 44% inside the tumor. The IT with 10 µg of proteins reduced the tumor volume by 60% while the treatment with associated proteins reduced the tumor volume by 73%. With regard to the tumor mass, we observed a reduction of 55 to 60% after IT with 10 µg of proteins, while for AP treatment this reduction was 63%. Greater evidence of the importance of simultaneous inhibition of integrins was observed with treatment using 5 µg of the proteins. The IT with 5 µg of proteins reduced the tumor volume by 41 to 47% and AP treatment reduced it by 65%. The IT with 5 µg of proteins reduced the tumor mass by 31% while with AP the reduction was 57%. The levels of plasma VEGF were reduced by 35% after IT with 10 µg of the proteins while with AP treatment the levels were reduced by 41%. Microvascular density was assessed by immunohistochemistry using anti-CD31. The mean number of vessels in the tumor was reduced by 60% after IT with 10 µg of proteins while by AP treatment the reduction was 78%. Simultaneous treatment with inhibitors of different integrins potentiate antiangiogenesis.