Objective To investigate the potential mechanism of follicular regulatory T (Tfr) cells in the pathogenesis of rheumatoid arthritis (RA). Methods The percentage of CD4+CXCR5+FOXP3+ICOS+ Tfr cells in the peripheral blood of 20 patients with RA and 20 healthy subjects were detected by flow cytometry, and the correlation between the proportion of Tfr cells and the clinical laboratory index of RA was analyzed. The serum levels of interleukin-10 (IL-10), IL-12, IL-2, transforming growth factor-β (TGF-β) and C-X-C motif chemokine ligand 13 (CXCL13) were measured by ELISA. The mRNA expression of Bcl6 and B lymphocyte induced mature protein 1 (Blimp-1) in peripheral blood mononuclear cells (PBMCs) was detected by real-time quantitative PCR. Immunohistochemistry was used to detect the expression of Bcl6 and CXCL13 in synovium of RA patients. Results The percentage of Tfr cells in the RA patients significantly decreased compared with the healthy controls, which was negatively related to the C reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), disease activity score in 28 joints (DAS28). The serum levels of IL-12 and CXCL13 in the patients with RA went up obviously, while the levels of IL-2, IL-10 and TGF-β went down remarkably. The Bcl6 mRNA level in PBMCs of the RA patients was significantly raised, while the expression of Blimp-1 mRNA was significantly reduced. Bcl6 and CXCL13 were highly expressed in the synovium of the RA patients. Conclusion The decrease of the proportion of Tfr cells in the peripheral blood may be related to the occurrence and development of RA.