We examined the role of Macrophage migration inhibitory factor (MIF) in the proliferation and differentiation of theepidermis. The expression of cytokeratin 14 increased in normal human epidermal kerationocytes (NHEKs) or HaCaT cells after the addition of recombinant MIF. On the other hand, we observed decrease expression of of filaggrin and transglutaminase 1 in NHEKs and HaCaT cells after the addition of recombinant MIF. The cell growth increased by the addition of MIF and decreased after the transfection of MIF siRNA. Furthermore, it was suggested that MIF might promote the proliferation and suppress the differentiation of epidermis via Rho-GTPase, PI3K and ERK1/2.