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Abstract: Objective To investigate the change of CD4+CD25+FoxP3+ regulatory T cells （Treg）in peripheral blood（PB）and synovial fluid（SF）in patients with rheumatoid arthritis（RA） and its role in RA immune tolerance imbalance. Methods The frequency of CD4+CD25+FoxP3+ Treg in PB and SF cells in active RA patients and healthy volunteers were determined using flow cytometry. The expression of FoxP3 gene in mononuclear cells was analyzed by real-time PCR. The correlation between the frequency of CD4+CD25+FoxP3+ Treg in PB cells and disease activity indices was evaluated. Results ① Active RA patients had a higher level of CD4+CD25+FoxP3+ Treg in SF cells (7.56%±2.89%) than in PB cells（1.84%±0.97%). Their level of CD4+CD25+FoxP3+ Treg in SF cells was also higher than that of healthy volunteers（2.19%±0.54%). Anti-CCP antibody (ACPA) positive RA patients had a lower level of CD4+CD25+FoxP3+ Treg (1.40%±0.63%) in PB cells compared with the ACPA negative RA patients (2.85%±0.87%). ② Active RA patients had a higher mRNA level of FoxP3 in SF mononuclear cells than those inactive RA patients and healthy volunteers (P+CD25+FoxP3+ Treg in PB cells in active RA patients had no correlation with disease activity indices（P>0.05）. Conclusion Altered frequency of CD4+CD25+FoxP3+ Treg in SF cells of RA patients might contribute to RA immune tolerance imbalance in inflammatory joints．