Angiopoietin-1 (Ang1) is a growth factor critical to the maturation of blood vessels. Through the binding to its tyrosine kinase receptor, Tie2/Tek, this factor is thought to play a role in stimulating endothelial cell survival, endothelial cell migration, and also to recruit pericytes. These mechanisms are critical to the sprouting of new blood vessels from pre-existing ones, a process known as angiogenesis. The present study explores the importance of Ang1 in liver angiogenesis by conditionally overexpressing human Ang1 in the hepatocytes of mice, thus modulating hepatic vasculature. Arterial sprouting, enlarged arteries, loss of portal veins from the portal triads, and capillarization of sinusoids was observed. Most importantly, these phenotypic changes were completely reversed within 14 days of cessation of transgene expression. Through these animal studies, the elucidation of the "context-dependent" activities of the angiopoietins on endothelial cells may result in the design of novel therapies that target the Angiopoietin/Tie2 pathway.