The homeostasis of the immune system depends on the balance between the immune response to an invaded pathogen and the immune tolerance to self antigens. Both central and peripheral tolerances are important mechanisms for the induction and maintenance of T cell tolerance. Recently, much attention has been paid to regulatory T cells (Treg), which play a significant role in maintaining peripheral immune tolerance. So far, there has been no satisfactory advance regarding the surface markers of Treg cells, as none is unique for Treg cells. In this review, we summarize some important molecules expressed in naturally occurring CD4+CD25+ Treg cells (nTreg), including forkhead/winged-helix family transcriptional repressor p3 (Foxp3), the tumor necrosis factor receptor (TNFR) family, CD28/CTLA4 molecules, chemokine receptors, Toll-like receptors (TLRs), membrane-bound TGF-βand other molecules, such as neuropilin-1, lymphocyte activation gene-3 (LAG)-3 and granzyme. This review provides a collective view on current studies of nTreg cell activation and development related to the expression of molecules and cell phenotype markers, which is important for elucidation of nTreg cell origin, development and function. The homeostasis of the immune system depends on the balance between the immune response to an invaded pathogen and the immune tolerance to self antigens. Both central and peripheral tolerances are important mechanisms for the induction and maintenance of T cell tolerance. paid to regulatory T cells (Treg), which play a significant role in peripheral immune tolerance. So far, there has been no satisfactory advance regarding the surface markers of Treg cells, as none is unique for Treg cells. In this review, we summarize some important molecules expressed in the naturally occurring CD4 + CD25 + Treg cells (nTregs), including forkhead / winged-helix family transcriptional repressor p3 (Foxp3), the tumor necrosis factor receptor (TNFR) family, CD28 / CTLA4 molecules, chemokine receptors, Toll -like receptors (TLRs), membrane-bound TGF-βand other molecules, such as neuropilin-1, lymphocyte activation gene-3 (LAG) -3 and granzyme. This review provides a colle ctive view on current studies of nTreg cell activation and development related to the expression of molecules and cell phenotype markers, which is important for elucidation of nTreg cell origin, development and function.