UV radiation-induced skin damages may result in pre-cancerous and cancerous skin lesions, and acceleration of skin aging. It involves an imbalance of the endogenous antioxidant system that leads to the increase of free radical levels and inflammation. Therefore, antioxidant supplementation might inhibit such imbalance. In this regard, quercetin is a promising drug, this plant derived lipophilic flavonoid presents the higher antioxidant activity among flavonoids and multiple antioxidant mechanisms. Thus, the present study investigated the possible beneficial effects of topical formulations containing quercetin to inhibit UVB irradiation-induced oxidative damages. Quercetin was administered on the dorsal skin of hairless mice using two formulations, formulation 1 (non-ionic emulsion with high lipid content) and formulation 2 (anionic emulsion with low lipid content). The UVB irradiation (0.31-3.69 J/cm(2)) induced a dose-dependent increase in the myeloperoxidase (MPO) activity (4-2708%) and depletion of reduced glutathione (GSH) (22-68%) in the skin of hairless mice after 6h. These results demonstrated that the UVB doses are not excessive, and additionally, they are lower than the doses used in other similar studies. Proteinases secretion/activity, detected by the qualitative sodium dodecyl sulphate polyacrylamide gel electrophoresis substrate-embedded enzymography (zymography), was also enhanced in the same manner as MPO activity using the UVB dose of 1.23J /cm(2). Formulations 1 and 2 inhibited the MPO activity increase (62% and 59%, respectively), GSH depletion (119% and 53%, respectively) and proteinases secretion/activity. To our knowledge, this is the first study to demonstrate the effectiveness of topical formulations containing quercetin to inhibit the UVB irradiation-induced skin damages. Thus, these data suggest the possible usefulness of topical formulations containing quercetin to prevent UVB radiation skin damages.