We examined that the protective effects of ANX1 on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammationin animal models using a Tat-ANX1 protein. Topicalapplication of the Tat-ANX1 protein markedly inhibited TPAinducedear edema and expression levels of cyclooxygenase-2(COX-2) as well as pro-inflammatory cytokines such as interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha(TNF-α). Also, application of Tat-ANX1 protein significantlyinhibited nuclear translocation of nuclear factor-kappa B(NF-κB) and phosphorylation of p38 and extracellular signalregulatedkinase (ERK) mitogen-activated protein kinase(MAPK) in TPA-treated mice ears. The results indicate thatTat-ANX1 protein inhibits the inflammatory response byblocking NF-κB and MAPK activation in TPA-induced miceears. Therefore, the Tat-ANX1 protein may be useful as atherapeutic agent against inflammatory skin diseases.