Objective Infliximab is a kind of recombinant human mouse chimeric anti-tumor necrosis factor monoclonal antibody. Here we aimed to examine the impact of infliximab therapy on RANK/RANKL/OPG system in the peripheral blood of rheumatoid arthritis (RA) patients. Methods Fifty patients with RA were rigorously screened and randomly divided into 2 groups. One group was treated with infliximab (3 mg/kg)and methotrexate (MTX). As control, the other group was treated with MTX alone. Infliximab was administered at weeks 0, 2, 6 and 14. The expression of RANK, RANKL mRNA in the peripheral blood, serum OPG and clinical indicators changes at week 0 and 18 were compared.x2-test or t-test were used for statistical analysis.Results After treated with infliximab, bone damage of joints were slowed down when examined by radiography in RA patients compared with the control group. And the ratio of OPG/RANKL was also decreased in RA peripheral blood (w0: 80.25;w 18: 63.2); (control group w0: 83.37; w18: 30.87)(P＞0.05). Although after the treatment with either MTX alone [w0: (238±15) pg/ml; w18: (118±10) pg/ml] or infliximab combined with MTX [(w0: (223.1±6.2) pg/ml; w18:(162.4±5.5) pg/ml], the serum levels of OPG were all decreased (P＞0.05), the level of OPG in infliximab treatment group was declined slower than those in the control group. Conclusion RA bone destruction can be inhibited by the combination therapy of infliximab and MTX. The mechanism may be partly through the RANK/RANKL/OPG system.