Interleukin‐2 (IL‐2) treatment is currently used to enhance T cell‐mediated immune responses against tumors or in viral infections. At the same time, IL‐2 is essential for the peripheral homeostasis of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg). In our study, we show that IL‐2 is also an important activator of Treg suppressive activity in vivo. IL‐2 treatment induces Treg expansion as well as IL‐10 production and increases their suppressive potential in vitro. Importantly, in vivo application of IL‐2 via gene‐gun vaccination using IL‐2 encoding DNA plasmids (pIL‐2) inhibited naive antigen‐specific T cell proliferation as well as a Th1‐induced delayed type hypersensitivity response. The suppressive effect can be transferred onto naive animals by Treg from IL‐2‐treated mice and the suppression depends on the synergistic action of IL‐10 and TGF‐β. These data highlight that during therapeutic treatment with IL‐2 the concomitant activation of Treg may indeed counteract the intended activation of cellular immunity.