Angiopoietins and Tie2 are angiogenic-specific ligand and receptor complex that have been shown to play a critical role in tumor angiogenesis. Angiopoietin-2 (Ang2) is one of four ligands for receptor Tie2 and it is the naturally occurring antagonist to Tie2, inhibiting the action of Angiopoietin-1 (Ang1). Over the last decade, significant research has focused on elucidating the role of Ang2 in cancer biology and its exact role in tumor angiogenesis remains elusive. In this study we have focused on establishing the role of Ang2 in angiogenesis of malignant astrocytomas. We have demonstrated that Ang2 significantly enhances the vascular growth of malignant astrocytomas and constant upregulation of Ang2 throughout all phases of tumor growth generates abnormal vascular structures that are not typically seen in human astrocytomas, suggesting that Ang2 plays a tumor stage-dependent role and is not a consistently elevated throughout all growth stages of malignant astroctyomas.