Angiogenesis, the process of formation of blood vessels, together with inflammation, is essential for tumor growth and metastasis. Macrophage recruitment and cytokine/chemokine production, growth factors and proteolytic enzymes is a common feature of inflammation, angiogenesis and cancer, and an important goal of a new approach to cancer treatment. Phenolic acids (gallic, caffeic and tannic acid) as natural phytochemicals and strong antioxidants show chemopreventive and therapeutic properties in cancer treatment. We investigated the effect of phenolic acids on tumor growth, angiogenesis, macrophage polarization and oxidative stress on the angiogenic model caused by ip inoculation of EAT cells (2.5x106) in Swiss albino mouse. The results show that phenolic acids exhibit immunostimulatory, anti-inflammatory, antiangiogenic and antitumor effects. The antitumor effect of phenolic acids is based on the cytotoxic efficacy of M1 macrophage, direct inhibition of EAT cell growth, inhibition of vascular endothelial growth factors (VEGF) and growth of blood vessels in the peritoneal cavity of EAT-bearing mice. Phenolic acids through the inhibition of proangiogenic factors, particularly VEGF, metalloproteinases 2 and 9 (MMP-2 and MMP-9) and cyclooxygenase 2 activity (COX-2), inhibit process of angiogenesis, tumor growth and increase survival of EAT-bearing mice. The antioxidant ability of phenolic components blocks the occurrence of M2 tumor associated macrophages (TAMs) and significantly inhibits tumorigenesis in mouse model. Based on the above, TAMs inhibition may be effective in the cancer treatment and other chronic diseases associated with process of angiogenesis.