To search for a new class of antidiabetic compounds, effects of 44 flavonoids on the adipogenesis of 3T3-L1 cells were examined. Among them, 3,4′,7-trimethylkaempferol, tetramethylkaempferol, and pentamethylquercetin concentration-dependently enhanced the accumulation of triglyceride, a marker of adipogenesis. With regard to structural requirements of flavonoids for the activity, it was fond that: (1) most flavonoids having hydroxy groups lacked the effect; (2) flavonols with methoxy groups showed stronger effects particularly those with a methoxy group at the 3-position; and (3) a methoxy group of flavonols at the B ring was also important. 3,4′,7-Trimethylkaempferol, tetramethylkaempferol, and pentamethylquercetin significantly increased the amount of adiponectin released into the medium and the uptake of 2-deoxyglucose into the cells. Furthermore, tetramethylkaempferol and pentamethylquercetin also increased mRNA levels of adiponectin, glucose transporter 4 (GLUT4), and fatty acid-binding protein (aP2). Both compounds also increased the mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ2 and CCAAT/enhancer-binding protein (C/EBP)α, β, and/or δ, although, different from troglitazone, they did not activate PPARγ directly in a nuclear receptor cofactor assay.