Objective To investigate the effect of before and after combination therapy of thalidomide and methotrexate (T+M) on regulatory T cells and IL-6 expression profile,and to reveal the mechanism of therapeutic effect of T+M on rheumatoid arthritis.Methods A total of 58 patients with rheumatoid arthritis from August 2014 to August 2016 in the Third Affiliated Hospital of Wenzhou Medical University.The flow cytometry assay and enzyme-linked immunosorbent assay (ELISA) were used to estimate the ratio of peripheral blood regulatory T cells and expression profile of IL-6 in peripheral blood lymphocyte before and after combination therapy of thalidomide and methotrexate .Results After combination therapy of T+M,the ratio of peripheral blood CD25 +Foxp3/CD4 +T cells had a marked increase compared with before combination of therapy of T +M;but the expression of IL-6 had a significant decrease in the group of after combination therapy of T +M compared with before combination therapy.Conclusion The effect of combination therapy of T+M on rheumatoid arthritis is associated with increasing the ratio of regulatory T cells and decreasing the secretion of IL-6 that could regulate T cells to homeostasis.