Apigenin, a plant flavenoid compound has been claimed for its antioxidant, anti inflammatory and recently antiangiogenic property. In this paper, the antiangiogenic activity of apigenin and selenium was tested in vitro as well as in vivo via systemic intramuscular injection targeting the improvement of cancer therapeutic protocols. The angiogenic regulators Matrix metalloproteinase 2 and 9( MMP2 and MMP9), the expression of tumor necrosis factor- α (TNF-α; Key cytokine) as well as the antioxidant markers catalase, superoxide dismutase and glutathione peroxidase (CAT, SOD and GPX) and DNA fragmentation were estimated to monitor efficacy of Apigenin and selenium in cancer treatment strategy. All parameters were determined as a time course on days 16 and 22 after tumor volume reached 1mm . The using of MTT assay on Ehrlich ascites carcinoma (EAC) cells in vitro showed that apigenin and /or selenium inhibit EAC cells proliferation. In vivo, Administration of apigenin and /or selenium to mice bearing tumor reduced significantly the TNF-α expression, MMP 2 and 9 levels and nitric oxide (NO) concentration while, increased the liver antioxidant enzymes (CAT, SOD and GPX) activities. The DNA fragmentation and the expression of antiangiogenic factors TIMP- in spleenocytes were significantly increased when compared with their values in mice bearing tumor. From the results obtained, it could be postulated that the synergistic administration of apigenin and selenium might improve the condition of cancer therapy via decreasing the tumor metastasis possibility in addition to increase cancer cells apoptotic transforming factors and conservation of normal cells antioxidant parameters.