OBJECTIVE： To study the effect of Xuchangqing-ermiaosan-santeng formula on the contents of tumor necrosis factor α （TNF-α） and ossification-related factor DKK-1 in serum of model mice with arthritis， and reveal its mechanism in the treatment of arthritis. METHODS： 60 BALB/c mice were randomly divided into normal group， model group， sulfasalazine group （positive control， 9 mg/kg） and Xuchangqing-ermiaosan-santeng formula low-dose， medium-dose， high-dose groups （calculated by crude drug as 11.25， 22.5， 45 g/kg）， 10 in each group. Except for normal group， other 50 mice were intraperitoneallly injected complete Freund’s adjuvant + proteoglycans to induce model with arthritis. After modeling， mice in each administration group were intragastrically administrated relevant medicines， mice in normal group and model group were intragastrically administrated equal volume of normal saline， once a day， for 20 d. After administration， enzyme-linked immunosorbent assay was used to detect the contents of TNF-α and DKK-1 in serum of mice in each group， and ultrastructural changes of sacroiliac joint synovial cells were observed by transmission electron microscopy. RESULTS： Compared with normal group， TNF-α content in serum in model group was obviously increased， DKK-1 content was obviously decreased （P＜0.05）； sacroiliac joint synovial cells showed hyperplasia， organellar deformation， mitochondrial swelling and other pathologic damage. Compared with model group， TNF-α contents in serum in each administration group were obviously decreased （P＜0.05 or P＜0.01）； except for sulfasalazine group， the DKK-1 content of mice in other administration groups were obviously increased （P＜0.05）. Pathologic damages of sacroiliac joint synovial cells in each administration group were reduced to varying degrees， and improvement degree in Xuchangqing-ermiaosan-santeng formula groups was higher than sulfasalazine group. CONCLUSIONS： Xuchangqing-ermiaosan-santeng formula may inhibit the sacroiliac arthritis and pathological ossification of model mice with arthritis by decreasing TNF-α content and increasing DKK-1 content in serum.