Flemingia macrophylla (Leguminosae), a native plant of Taiwan, is used as folk medicine. An in vitro study showed that a 75% ethanolic extract of F. macrophylla (FME) inhibited osteoclast differentiation of cultured rat bone marrow cells, and the active component, lespedezaflavanone A (LDF-A), was isolated. It was found that oral administration of FME for 13 weeks suppressed bone loss in ovariectomized rats, an experimental model of osteoporosis. In addition, FME decreased urinary deoxypyridinoline concentrations but did not inhibit serum alkaline phosphatase activities, indicating that it ameliorated bone loss via inhibition of bone resorption. These results suggest that FME may represent a useful remedy for the treatment of bone resorption diseases, such as osteoporosis. In addition, LDF-A could be used as a marker compound to control the quality of FME.