Background:　Destructive　erosion　of　bone　or　osteolysis　is　a　major　complication　of　inflammatory　conditions　such　as　rheumatoid　arthritis　(RA),　periodontal　disease,　and　periprosthetic　osteolysis.　Natural　plant-derived　products　have　received　recent　attention　as　potential　therapeutic　and　preventative　drugs　in　human　disease.　Methods:　The　effect　of　Angelica　sinensis　(AS)　extract　on　RANKL-induced　osteoclast　differentiation　was　examined　in　this　study.　The　osteoclast　precursor　cell　line　bone　marrow　macrophages　(BMMs)　was　cultured　and　stimulated　with　RANKL　followed　by　treatment　with　AS　at　several　doses.　Gene　expression　profiles　of　c-Fos,　c-Jun,　NFATc1,　TRAP,　and　OSCAR　were　sequentially　evaluated.　Results:　AS　extract　inhibited　RANKL-mediated　osteoclast　differentiation　in　BMMs　in　a　dose-dependent　manner　without　any　evidence　of　cytotoxicity.　AS　extract　strongly　inhibited　p38,　ERK,　JNK,　p65　phosphorylation　and　I-kappa　B　degradation　in　RANKL-stimulated　BMMs.　AS　extract　also　inhibited　the　mRNA　expression　of　c-Fos,　c-Jun,　NFATc1,　TRAP,　and　OSCAR　in　RANKL-treated　BMMs.　Moreover,　RANKL-induced　c-Fos,　c-Jun　and　NFATc1　protein　expression　was　suppressed　by　AS　extract.　Conclusions:　These　results　collectively　suggested　that　AS　extract　demonstrated　inhibitory　effects　on　RANKL-mediated　osteoclast　differentiation　in　bone　marrow　macrophages　in　vitro,　indicating　that　AS　may　therefore　serve　as　a　useful　drug　in　the　prevention　of　bone　loss.