Recent studies in infectious disease and autoimmune disease models have revealed that interleukin (IL)-22 might have both proinflammatory and anti-inflammatory functions. There is, however, lack of evidence for IL-22 directly repressing immune responses of leukocytes. We propose that IL-22 promotes innate immunity of tissues, as well as repairing and healing mechanisms during inflammation. Consequently, the restoration of tissue homeostasis helps to attenuate the inflammatory responses involving various immune cells.