OBJECTIVE TACI-Ig, a BlyS inhibitor, is a new biologic agent in treatment for RA.The effective differences of TACI-Ig with old biologic agents (TNF-ct inhibitors) and conventional DMARDs remain unclear.In this study, the different efficacies of TACI-Ig with RhTNFR:Fc and methotrexate (MTX) were compared in collagen-induced arthritis (CIA) mice.MEHTODS CIA model was established in DBA/1 mice.CIA mice were divided into TACI-Ig (9 mg·kg-1), rhTNFR:Fc (4 mg·kg-1), MTX (4 mg · kg-1) and IgG-Fc (9 mg·kg-1) groups.CIA mice in TACI-Ig, rhTNFR:Fc and IgG-Fc were given medication (intraperitoneal injection, three times per week, medicate 6 weeks) when the onset of arthritis were observed.CIA mice of MTX (4 mg·kg-1) group were given the intragastric administration, once per week, medicate 6 weeks.Meanwhile, normal control and CIA model were given.The different efficacies of comparative drugs were evaluated by the analyses of ankle joints and spleens pathology, cytokines, subsets of T and B lymphocytes, and so on.RESULTS (1) TACI-Ig and RhTNFR: Fc reduced arthritis scores seven days later than that of MTX.(2) TACI-Ig and MTX were superior to RhTNFR: Fc in reduction synovial hyperplasia and cell infiltration scores.(3) TACI-Ig and MTX had higher efficacy than RhTNFR:Fc on lymphoid follicular hyperplasia, germinal centers and red pulp scores.(4) TACI-Ig and MTX have higher efficacies than RhTNFR:Fc on BlyS, but TACI-Ig was inferior to RhTNFR:Fc in reduction TNF-α.TACI-Ig and MTX could reduce significantly IgA and IgM, RhTNFR: Fc had no effects on them.(5) In TACI-Ig and MTX-treated mice, the expression of CD20 was significantly lower than that in CIA mice, but RhTNFR: Fc had no obvious effect on CD20 expression.(6)TACI-Ig, RhTNFR : Fc and MTX showed a significant reduction in the percentages of CD4 + CD25 + and CD4 + CD154 + T cells, TACI-Ig was more efiicacy than RhTNFR : Fc in decrease CD4 + CD154 + T cell.TACI-Ig and MTX treatment also resulted in a significant reduction in the percentages of CD4 + CD69 + , RhTNFR : Fc but had no effects on CD4 + CD69 +.All TACI-Ig, RhTNFR: Fc and MTX increase the percentage of CD4 + CD62L+ T cells.TACI-Ig and MTX were superior to RhTNFR:Fc in enhance CD4+ CD62L+ T cells.(7) TACI-Ig and MTX could reduce the percentage of CD19 + IgD + and CD19 + CD21 + B cells, but RhTNFR:Fc had no obvious effect on the percentage of CD19 + IgD + and CD19 + CD21 + B cells.CONCLUSION TACI-Ig is as effective as rhTNFR:Fc and MTX on CIA mice by improving joint and spleen pathology, regulating T and B lymphocytes function, although different effective mechanisms among them.This study would be useful for treatment selection of RA in different pathological condition.