There are two types of angiogenesis, sprouting angiogenesis and intussusceptive angiogenesis. Sprouting angiogenesis, the outgrowth of a new branch from an existing vessel, is a process that has been well characterized using numerous model systems. Intussusceptive angiogenesis, splitting of an existing vessel, starts with the formation of an intraluminal vascular pillar. The cellular interactions and molecular mechanisms regulating vascular pillar formation are largely unknown. An increased understanding of intussusceptive angiogenesis requires the development of observable, manipulable model systems to study vascular pillar formation. We have established a cell culture model of vascular pillar formation in an endothelial cell-smooth muscle cell co-culture system. Vascular pillar formation was inhibited by broad spectrum matrix metalloproteinase inhibitors.