Two 3-phenyldihydroisocoumarins (hydrangenol and phyllodulcin), a 3-phenylisocoumarin (thunberginol A), and a stilbene (hydrangeaic acid) from the processed leaves of Hydrangea macrophylla var. thunbergii (Hydrangeae Dulcis Folium) promoted adipogenesis of 3T3-L1 cells. Hydrangenol, a principal constituent, significantly increased the amount of adiponectin released into the medium and mRNA levels of adiponectin, peroxisome proliferator-activated receptor gamma2 (PPARgamma2), and glucose transporter 4 (GLUT4), while it decreased the expression of interleukin 6 (IL-6) mRNA. Furthermore, hydrangenol significantly lowered blood glucose and free fatty acid levels 2 weeks after its administration at a dose of 200 mg/kg/d in KK-A(y) mice.