The seaweed Ecklonia cava, a brown algae abundant in JeJu Island, South Korea, has large amounts of the polyphenol compound phloroglucinol (PG, 1,3,5-trihydroxybenzene), which has been proposed to exert interesting biological properties including antioxidant and radioprotective effects against ionizing radiation-induced damages in various cells and tissues. To identify antioxidant and radioprotective effects of PG in skin tissues, we exposed mice to 8.5 Gy whole body irradiation (WBI) at day 6 after depilation with and without PG treatment. In PG treated cases, PG was applied twice, once at 17.8 hours before and then at the time of WBI. At 8 hours after WBI, a reduction in the formation of thiobarbituric acid-reactive substrates (TBARS) was observed in the PG treated group. Upon western blot analysis, PG treatment overexpressed the MnSOD, catalase, and GPx-1, although the difference was not significant. In parallel with the results of western blot analysis, the percentage of MnSOD-and catalase-positive cells was significantly increased at 8 and 24 hours after WBI, while no significant difference was observed over 48 hours in PG treated skins. Moreover, PG treatment increased the percentage of Ki-67 positive cells compared with that of irradiated only mice at 8 hours after WBI. Our results suggest that PG is effective at attenuating oxidative stress, and that the promotion of antioxidant enzymes such as MnSOD and catalase may be an important aspect for its radioprotection in skin.