Abstract: The relationship between RANKL/OPG(receptor activator of nuclear factor-κB ligand/ osteoprotegerin) system and type Ⅱcollagen-induced arthritis in rats and the effects of ⁹⁹Tc-methylene diphosphonate (⁹⁹Tc-MDP) were explored. The collagen-induced arthritis (CIA) model was established by subcutaneous injection with type Ⅱ collagen and complete Freud’s adjuvant to rats,except the normal group (n=8).The rats that successfully developed CIA(n=24) were divided into three groups randomly:model group (n=8),⁹⁹Tc-MDP-treated group (n=8) and methotrexate (MTX)-treated group (n=8).The severity of arthritis was quantitated by measurement of arthritis index;the levels of RANKL/OPG in synovial fluid were tested by ELISA;and the expression of RANKL/OPG on synovial membrane was tested by immunohistochemistry. The arthritis index,the concentrations of RANKL and OPG in synovial fluid and their expression on synovial membrane increased in model group,⁹⁹Tc-MDP-treated group and MTX-treated group compared with normal group (P<0.01).⁹⁹Tc-MDP and MTX treatment prevented the increase of all indexes above (P<0.01),furthermore,the indexes in ⁹⁹Tc-MDP-treated group were notably lower than those of the MTX-treated group (P<0.01).It was concluded that RANKL and OPG played a role in lesions of synovial membrane,cartilage and bone of CIA rats,and that ⁹⁹Tc-MDP might relieve the injury of synovial membrane,cartilage and bone through inhibiting the expression of RANKL and OPG and decreasing the ratio of RANKL/OPG,and ⁹⁹Tc-MDP was better than MTX in relieving synovial lesions,cartilage damage and bone erosion.