Abstract: Tong Yunlei, Chen Ming, Gong Yu, Zhang Lingling, Yu Qian, Wang Yao, Shi Yuling Department of Dermatology, Tenth People′s Hospital of Tongji University, Shanghai 200072, China （Tong YL, Gong Y, Zhang LL, Yu Q, Wang Y, Shi YL）; Department of Physical Examination, Tenth People′s Hospital of Tongji University, Shanghai 200072, China （Chen M） Corresponding author: Shi Yuling, Email: shiyuling1973@tongji.edu.cn 【Abstract】 Objective To evaluate the effect of recombinant human tumor necrosis factor receptor type Ⅱ: IgG Fc fusion protein （rhTNFR:Fc, trade name Etanercept） combined with methotrexate on levels of interleukin-17A （IL-17A） and tumor necrosis factor-α （TNF-α） in the serum and mononuclear cells of patients with moderate to severe plaque psoriasis. Methods A total of 30 patients with moderate to severe plaque psoriasis were enrolled from Department of Dermatology of Tenth People′s Hospital of Tongji University between August 2014 and February 2016, and then were randomly and equally divided into Etanercept group and Etanercept + methotrexate group. The treatment lasted 24 weeks. Fifteen healthy blood donors served as healthy control group. Enzyme-linked immunosorbent assay （ELISA） and real-time quantitative PCR were performed to measure the serum levels and mRNA of IL-17A and TNF-α, respectively, in the patients of the above two groups before and after the treatment. Results Before the treatment, the serum levels of IL-17A and TNF-α, as well as the mRNA of IL-17A and TNF-α in peripheral blood mononuclear cells （PBMCs）, were all significantly higher in all the patients than in the healthy controls （all P < 0.05）. After the treatment, compared with the Etanercept group, the Etanercept + methotrexate group showed significantly lower serum levels of IL-17A （142.67 ± 14.82 vs. 163.54 ± 23.18, P < 0.05） and TNF-α （70.07 ± 25.02 vs. 91.98 ± 14.62, P < 0.05）, as well as lower mRNA of IL-17A （1.12 ± 0.33 vs. 1.56 ± 0.77, P < 0.05） and TNF-α in PBMCs （2.50 ± 1.04 vs. 3.61 ± 2.14, P < 0.05）. Conclusion Etanercept combined with methotrexate is superior to Etanercept alone in the treatment of psoriasis, and can reduce treatment duration and improve therapeutic effect, likely by down-regulating the of IL-17A and TNF-α.