Abstract Obesity, soft tissue wound healing, adipose tissue engineering, lipomas, and other physiological and pathophysiological conditions necessitate a clear understanding of the interactions between adipocytes and endothelial cells. Adipogenesis and angiogenesis are intimately integrated, despite not being in direct apposition with one another. However, underlying mechanisms have not been elucidated. In this study, the interactions of preadipocytes (PAs) and microvascular endothelial cells are investigated under varying defined O2 conditions, using a coculture system. Results clearly demonstrate that endothelial cells release a soluble factor that sustains PAs viability under hypoxic conditions. Vascular endothelial cell growth factor is not the potential soluble factor (data not shown).