Development of obesity is associated with substantial modulation of adipose tissue structure, involving adipogenesis, angiogenesis, and extracellular matrix remodelling. These processes require proteolytic activity, provided mainly by the fibrinolytic (plasminogen/plasmin), matrix metalloproteinase, and ADAM/ADAMTS systems. In early-stage development of adipose tissue, adipogenesis is tightly associated with angiogenesis. Thus, adipose tissue explants trigger blood vessel formation, and in turn adipose tissue endothelial cells promote pre-adipocyte differentiation. Modulation of angiogenesis and of proteolytic systems may have the potential to impair adipose tissue development.