Human embryonic stem (hES) cells are undifferentiated and pluripotent cells that hold great therapeutic potential, but are hampered by our limited knowledge to promote specific cell differentiation. Here we provide the first report of the directed differentiation of hES cells into adipocytes. Embryoid bodies (EBs) derived from hES cells are shown to respond to factors that promote adipogenesis. Differentiated cells were observed that displayed the key features of adipocytes, i.e., expression of specific molecular markers, such as peroxisome proliferator-activated receptor gamma2 (PPARgamma2), adipocyte fatty acid binding protein (aP2) and adiponectin, the secretion of leptin, and the accumulation of lipid droplets in cytoplasm. Taken together, our results demonstrate that adipocytes derived from hES cells in vitro can provide a novel model system to study human adipogenesis and obesity.