Objective To investigate the possible roles of cellular immunosuppression induced by phenotypic and functional changes of peripheral CD4+CD25+ regulatory T cells (Tregs) in the pathogenesis of condylomata acuminata. Methods Three-color flow cytometry was performed to examine the expression of transcription factor Foxp3 in, along with several inhibitory membrane molecules, i.e. cytotoxic T lympho-cyte associated antigen-4 (CTLA-4), glucocorticoid-induced TNF receptor family-related gene (GITR) and programmed death-1 (PD-1) on peripheral CD4+CD25+ T cells from 46 patients with condylomata acuminata and 43 normal human controls. Meanwhile, high purity of CD4+CD25+ T cells were isolated from peripheral blood using imrnunomagnetic beads, and stimulated to produce intracellular suppressor cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), which were detected by flow tyro-metric analysis. Results The number of peripheral CD4+CD25+ Foxp3+ Tregs increased significantly in patients with condylomata acuminata than that in the normal controls (7.37% ± 2.43% vs 5.96% ± 2.09%,P ＜ 0.001). The expressions of CTLA-4 and PD-1 were 1.86% ± 1.13% and 2.41% ± 1.12%, respectively,in the patients, which were significantly higher than those in the normal controls(1.36% ± 0.90% and 1.70%± 0.97%, P ＜ 0.05 and 0.01, respectively). The number of TGF-beta-positive CD4+CD25+ T ceils from peripheral blood were increased in patients than that in, the controls (1.57% ± 0.91% vs 0.78% ± 0.24%, P ＜0.001). Conclusions Human papillomavirus infection can induce the activation and proliferation of CD4+CD25+ Tregs, enhance the expression of negative costimulatory molecules and secretion of suppressor cytokines, and inhibit antiviral immune response through multiple mechanisms.