Aim Paeoniflorin (Pae) is the principal bioactive component of total glucosides of peony (TGP),which has been widely used in therapy for rheumatoid arthritis (RA).Paeoniflorin6′Obenzene sulfonate (code:CP25), a novel compound that is a newly ester derivatives of Pae, was evaluated in rats with adjuvantinduced arthritis (AA) to study its potential antiarthritic activity.Methods AA rats were randomly divided into different groups and then treated with CP25 (25, 50, 100 mg · kg1) and methotrexate (0.5 ng · kg1), from day 16 to day 32 after immunization.Arthritis severity was evaluated by clinical manifestation and histopathological examination.The cells proliferation was determined by CCK8 assay.Activities of IL1β, IL6, IL17, IL10, TGFβ1,TNFα, RANKL and OPG were assessed by ELISA.The subsets of CD4 +T cells were assayed by flow cytometry.Results CP25 treatment effectively reduced clinical severity scores and blinded histopathological scores compared with AA groups.CP25treated rats exhibited a decrease in the proinflammatory cytokines (IL1 β, IL6, IL17,and TNFα), coupled with an increase in the antiinflammatory cytokines IL10 and TGFβ1 in serum and macrophages of AA rats.The flow cytometry analyses of CD4 + T cells dramatically demonstrated the immunomodulatory effects of CP25 on abnormal immune dysfunction.Apart from the antiinflammatory activity, treatment with CP25inhibited the fibroblastlike synoviocyte (FLS) activation and function.Furthermore, CP25 treatment of AA rats restored the balance between RANKL and OPG in favor of its antiosteoclastic effects.Conclusions Data presented here demonstrated that administration of CP25 significantly inhibited the progression of rat AA, with reductions both in arthritic inflammation and bone damage.The protective effects of CP25 in AA highlight an attribute that is potential as an ideal new antiarthritic agent for the treatment with human RA.