Total glucosides of paeony (TGP) are active compounds extracted from the roots of Paeonia lactiflora Pall. In this study, we investigated the mechanisms of total glucosides of paeony (TGP) in the treatment of adjuvant arthritis (AA). AA in rats was established. Synoviocytes proliferation and activity of IL-1 were determined by 3-(4, 5-2dimethylthiazal-2yl) 2, 5-diphenyltetrazoliumbromide (MTT) assay. Tumor necrosis factor alpha (TNF-alpha) and prostaglandin E2 (PGE2) were measured by radioimmunoassay. Ultrastructure of synovioctes was observed under transmission electron microscope. Phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulating kinase (ERK) and p38 kinase and expression of matrix metalloproteinases (MMPs) were detected by Western blot analysis. TGP (25, 50 and 100 mg kg(-1), ig, days 14-21) inhibited secondary inflammatory reaction, bone destruction and ultrastructure change of synoviocytes in AA rats. The administration of TGP (50 and 100 mg/kg, ig, days 14-21) in AA rats significantly decreased the production of IL-1, PGE2 and TNF-alpha by macrophage-like synoviocytes (MLS). TGP (25 mg/kg) also decreased the production of PGE(2) by MLS in AA rats. Furthermore, the increased phosphorylation of MAPKs, cell proliferation, and MMPs expression in fibroblast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats could also be inhibited by TGP (50 and 100 mg/kg, ig, days 14-21). The results suggest that TGP possesses anti-inflammatory effects by modulating the pro-inflammatory mediators production from MLS and phosphorylation of MAPKs from FLS.