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Ultraviolet irradiation (UV) can induce topical or systemic immunosuppression on skin, but its nature remains unknown. It is hypothesized that in topic immunosuppression, the iC3b-Mo/Mph-mitogen-activated protein kinase (MAPK) signal transduciton pathway induces the phosphorylation of extracellular signal-related kinase p44/42, which in turn causes the production of high levels of IL-10, and accelerates the transformation of mononuclear macrophages to macrophages that could clean out necrotic cells; at the same time, the phosphorylated p38 MAPK and production of IL-12 were inhibited, which hampers the differentiation and maturation of mononuclear macrophages to CD1c�� dendritic cells, and subsequently suppresses T cell-mediated immune response. The UV-induced systemic immunosuppression seems not to be realized by the direct decrease in the number and function of dendritic cells��but via the suppression of dendritic cell-induced Th1 immune response by activated B cells in draining lymph node.