In this study, we investigated the anti-inflammatory activity of water extract from Citru unshiu Macrow peels (WCP) in 12-0- Tetradecanoylphorbol acetate (TPA)-induced mouse ear edema model. First, we identified the phenolic compounds of WCP using HPLC analysis. As a results, WCP is composed of major compounds such as hesperidin and ferulic acid and sinapic acid, as well as minor compounds of coumaric acid, neo hesperidin and quercetin. In addition, WCP significantly decreased the ear thickness by reducing the epidermal and dermal thickness increased by TPA. Interestingly, treatment with TPA increased the expression levels of pro-inflammatory cytokine such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in mouse ear, they were effectively inhibited by the application of WCP. Moreover, WCP led to the decreased protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) induced by TPA-induced in mouse ear edema model. Taken together, we suggest that WCP could be considered as an effective anti-inflammatory material with its anti-inflammatory activity.