CD161 is used as a surrogate marker for Th17 cells, which are implicated in the pathogenesis of rheumatoid arthritis (RA). In this study, we evaluated the percentage, clinical significance, and CD98 and CD147 expression of CD4CD161 T cells. The potential role of CD147 and CD98 in cyclophilin A-induced chemotaxis of CD4CD161 T cells was analyzed. Thirty-seven RA patients, 15 paired synovial fluid (SF) of RA, and 22 healthy controls were recruited. The cell populations and surface expression of CD98 and CD147 were analyzed by flow cytometry. Spearman's rank correlation coefficient and multiple linear regression were applied to calculate the correlations. Chemotaxis assay was used to investigate CD4CD161 T cell migration. We found that the percentage of CD4CD161 T cells and their expression of CD147 and CD98 in SF were higher than in the peripheral blood of RA patients. Percentage of SF CD4CD161 T cells was positively correlated with 28-Joint Disease Activity Score (DAS28). CD147 monoclonal antibody (HAb18) attenuated the chemotactic ability of CD4CD161 T cells. An increased CD4CD161 T cell percentage and expression of CD147 and CD98 were shown in RA SF. Percentage of SF CD4CD161 T cells can be used as a predictive marker of disease activity in RA. CD147 block significantly decreased the chemotactic index of CD4CD161 cells induced by cyclophilin A (CypA). These results imply that the accumulation of CD4CD161 T cells in SF and their high expression of CD147 may be associated with CypA-mediated chemotaxis and contribute to local inflammation in RA.