Objective: To investigate the role of cyclosporin A (CsA) and methotrexate (MTX) combined therapy in modulation of serum IL-17 express in the patients with rheumatoid arthritis (RA). Methods: 83 new patients with rheumatoid arthritis were collected, which consist of MTX monotherapy (41 cases) and combination of MTX and CsA therapy (42 cases). The MTX dose was applied for 10~15 mg per week, and CsA was 3 mg/kg per day. The sera IL-17 expression was detected by ELISA before therapy and after 3 months treatment. In addition, disease activity index, RF and anti-CCP were also evaluated, and corelation between IL-17 and above clinical parameters were analyzed. Results: The levels of IL-17 in RA patients and healthy volunteers were analyzed. As compared with healthy control, RA patients have high level of IL-17 (P<0.001), two group RA patients has no difference. Interestingly, when compared with pre-treatment, the expression of IL-17 was significantly decreased in RA patients with MTX and CsA treatment (P=0.016), while MTX monotherapy has no considerable change (P=0.062). In the MTX and CsA treated group, correlations between the difference of IL-17 and those of clinical and laboratory parameters at baseline and 3 months from initial treatment showed significant correlation with anti-CCP (r=0.42, P=0.041) and DAS28 (r=0.49, P=0.023). Conclusion: The mechanism of CsA and MTX combined therapy in the patients with rheumatoid arthritis might due to the inhibition of IL-17 expression.