Rheumatoid　arthritis　(RA)　is　a　chronic　autoimmune　disease　characterized　by　synovial　inflammation　and　progressive　cartilage　and　bone　damage.　In　our　previous　studies,　we　found　that　Au　clusters　using　glutathione　as　a　template　(GACs)　produced　profound　anti-inflammatory　effects　in　vitro　on　lipopolysaccharide　(LPS)-induced　inflammation　in　mouse　macrophage　RAW　264.7　cells　and　type　II　collagen-induced　rat　RA　in　vivo.　In　this　study,　we　examined　whether　the　template　for　Au　clusters　synthesis　has　an　effect　on　its　anti-inflammatory　effect　and　whether　Au　nanoparticles　with　larger　particle　diameter　produce　the　same　anti-inflammatory　effect.　We　synthesized　Au　clusters　with　bovine　serum　albumin　(BSA)　as　a　template　(BACs),　Au　clusters　with　glutathione　(GSH)　as　a　template　(GACs),　and　Au　nanoparticles　with　glutathione　as　a　template　(GANs)　and　compared　their　anti-inflammatory　effects　in　vitro　and　in　vivo.　These　three　Au　nanomaterials　can　inhibit　the　production　of　lipopolysaccharide　(LPS)-induced　proinflammatory　mediators　and　ameliorate　type　II　collagen-induced　rat　RA.　However,　although　the　three　Au　nanomaterials　produced　similar　anti-inflammatory　effects,　the　GANs　with　larger　particle　sizes　were　less　stable　in　vivo　and　accumulated　in　the　peritoneum　after　intraperitoneal　injection,　resulting　in　poor　absorption　in　vivo.　The　BACs　showed　relatively　high　liver　accumulation　due　to　the　larger　molecular　weight　of　the　outer　shell.　Therefore,　we　believe　that　the　GACs　are　potential　reliable　nanodrugs　for　the　treatment　of　RA.