Bee venom (BV) has been used to treat diseases such as arthritis, rheumatism and pain in many countries. Although BV has recently been used as an additive of functional cosmetics, there is no evidence of the effects of BVon skin inflammation or disease. Here, we show that BV patch attachment or intra-peritoneal injection inhibited in vivo acute inflammation induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) using the mouse ear model of inflammation. When we examined the TNF-alpha and IL-1 beta mRNA expression in BV treated ear samples by real time PCR, even though BV treatment had no significant effects, it inhibited TNF-alpha and IL-1 beta mRNA expression when compared to samples treated with TPA alone. BV also inhibited edema (based on ear weight) and inhibited neutrophil infiltration (based on myeloperoxidase (MPO) activity measured as a neutrophil marker). Taken together, these results showed that BV exerted an anti-inflammatory effect in vivo and was beneficial in an animal model of skin inflammation. These results suggest that BV might be beneficial as a topical agent for the treatment of skin inflammation.