OBJECTIVE： To compare the effects of iguratimod combined with methotrexate and diacerein respectively on related indexes of refractory rheumatoid arthritis （RRA）. METHODS： 98 RRA patients were randomly divided into control group （48 cases） and observation group （50 cases）. Control group received Iguratimod tablet 25 mg， twice a day+Methotrexate tablet with initial dose of 10 mg， once a week， increased to 12.5 mg after 2 weeks， increased to 15 mg in the second courses， once a week. Observation group received Iguratimod tablet （the same dosage and usage with control group）+Diacerein granule 50 mg， twice a day. 4-week was a course， they were treated for 6 courses. Morning stiffness time， the numbers of 28 joints tenderness and swelling， 28 joint disease activity score （DAS28）， erythrocyte sedimentation rate （ESR）， rheumatoid factor （RF）， IL-1， vascular endothelial growth factor （VEGF）， tumor necrosis factor （TNF） -α， C-reaction protein （CRP）， malondialdehyde （MDA）， superoxide dismutase （SOD）， total antioxidant capacity （TAOC）， early peak flow （peak E）， left ventricular late flow peak flow （peak A）， E/A and left ventricular ejection fraction （LVEF） before and after treatment， and the incidence of adverse reactions in 2 groups were observed. RESULTS： Before treatment， morning stiffness time， the numbers of 28 joints tenderness and swelling， DAS28 score， ESR， RF， IL-1， TNF-α， CRP， VEGF， MDA， TAOC and peak A in 2 groups were significantly lower than before treatment， and observation group was significantly lower than control group； SOD， peak E， E/A and LVEF in 2 groups were significantly higher than before treatment， and observation group was significantly higher than control group， with statistical significances （P＜0.05）. And there was no significant difference in the incidence of adverse reactions （P＞0.05）. CONCLUSIONS： Iguratimod combined with diacerein is superior to iguratimod combined with methotrexate in improving cardiac function， oxidation-antioxidant imbalance play and reducing inflammatory reactions in the treatment of RRA， with similar safety.