CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) have been shown to play a regulatory or suppressive role in the immune response and are possibly relevant to the pathogenesis of autoimmune diseases. In the present study, we attempted to investigate the frequency of CD4+CD25+ Tregs in peripheral blood (PB) of collagen-induced arthritis (CIA) rats during the development of arthritis, to determine whether their frequency is involved in the immunoregulation of this disease. The results showed that normal rats had similar frequencies of CD4+CD25+ Tregs in PB during the experiment time, expressed as a percentage of CD4+CD25+Foxp3+ T cells among the CD4+ T lymphocyte po-pulation. In contrast, the frequency of CD4+CD25+Foxp3+ T cells in CIA rats was found to change du-ring the development of arthritis. In CIA rats, there is a significant negative correlation between the frequency of CD4+CD25+Foxp3+ T cells and paw swelling (r=−0.786, p＜0.01). The relationship between the frequency of CD4+CD25+Foxp3+ T and immune activation was not found in normal rats. During the time course, the frequency of CD4+CD25+Foxp3+ T was lower in CIA rats than in normal ones. The data suggest that the frequency of PB CD4+CD25+ Tregs may be a promising marker for arthritis activity.