In comparison with lightly pigmented skin, darkly pigmented skin displays superior permeability barrier function, possibly resulting from the reduced pH in the stratum corneum (SC) because acidification of lightly pigmented SC enhances barrier function comparable to darkly pigmented levels. Both permeability barrier and pH influence cutaneous inflammation. Whether pigmentation affects cutaneous inflammation is unknown. We demonstrated that 1) pigmented skin (SKH2/J) increased inflammatory threshold in both irritant and allergic contact dermatitis models induced by topical TPA and oxazolone ,respectively; 2) depigmentation of pigmented skin with hydroquinone lowered inflammatory threshold, which was accompanied by the increased expression levels of epidermal mRNA and protein for IL-1α, IL-1β, and TNFα; 3) acidification of non-pigmented skin (SKH1) with topical lactobionic acid increased inflammatory threshold, and normalized epidermal functions in both irritant and allergic contact dermatitis models. Together, these results suggest that epidermal hyperpigmentation reduces cutaneous sensitive to inflammatory stimuli, which is likely attributed to the acidification of SC by melanin.