Vascular endothelial growth factor (VEGF) is an important angiogenic factor and is expressed in wide variety of cell types. In this study, we investigated the mechanism of VEGF production in adipocytes in three sets of experiments. First, to clarify the relation between plasma VEGF concentrations and their expressions in adipose tissues, we investigated the genetically obese db/db and KK-Ay mice. Plasma VEGF concentrations in obese mice were significantly higher than in control and were related to adiposity. VEGF expressions in visceral fat were enhanced during growth and were related to fat deposition. Next, to demonstrate the relation between VEGF production and lipid accumulation in adipocytes, we analyzed VEGF mRNA expression and its protein secretion in 3T3-L1 cells. VEGF production was enhanced during lipid accumulation in 3T3-L1 cells after adipocyte conversion. Next, to clarify the role of anatomic localization on VEGF expression in adipocytes, we implanted 3T3-L1 cells into visceral or subcutaneous fat in athymic mice. 3T3-L1 cells implanted into the mesenteric area expressed more VEGF mRNA than that into the subcutaneous area. Plasma VEGF concentration in the mice implanted in visceral fat was higher than in controls. These results suggest that both the anatomic localization and the lipid accumulation are important for the VEGF production in adipocytes.