Mounting evidence demonstrates that the formation of new blood vessels, termed angiogenesis, plays critical roles in human disease development and progression. Based on these findings, there has been a tremendous effort to investigate the molecular mechanisms that drive blood vessel growth in adult tissues. Compared to physiological angiogenesis, inflammation is often accompanied with pathological angiogenesis and often is the underlying causes of many diseases such as cancer, arthritis, atherosclerosis, and others. Inflammation induces angiogenesis and reciprocally, angiogenesis facilitate inflammation. A study of the interaction between angiogenesis and inflammation will enhance our understanding of the mechanisms of diseases. It may generate novel approaches for therapy. Tie2 was recently identified as a receptor tyrosine kinase expressed principally on vascular endothelium, making it an attractive molecular target for angiogenic therapy. This review discusses the regulation of Tie2 and its angiopoietin ligand family in inflammation-associated angiogenesis focusing on cancer, arthritis, and atherosclerosis. The complexity of angiogenesis and context-dependent regulation of angiopoietin/Tie2 signaling in angiogenesis requires further studies.