This study was conducted for evaluation of the alleviating effects of Phellodendrin cortex water extract (PCWE) on skin inflammation in hairless mice. Skin inflammation was induced by UVB irradiation and application of squalene monohydroperoxide (Sq-OOH) to the back skin of hairless mice for six weeks. At the same time, saline (C), jojoba oil (VC), PCWE (E), and 0.01% retinoic acid diluted with polyethylene glycol (PC) were applied topically twice per day, six days per week for a period of six weeks. The skin erythema index of the E group was lower than that of the C group. Epidermis and dermis of the C group were remarkably thickened, compared to the PC or E group. In the C group, infiltration of many inflammatory cells, including neutrophils and lymphocytes, was observed in dermis, and a large number of mast cells were observed in dermis and hypodermis; the degree of degranulation was remarkable. However, these phenomena were alleviated in the PC and E2 groups. The E group showed a lower activity in skin xanthine oxidase but a higher activity in skin superoxide dismutase, compared to the C group (P<0.05). The VC, PC, and E groups also showed a high activity of skin catalase by 25.3%, 58%, and 42%, respectively, compared to the C group. Taken together, these results indicate that PCWE could have an alleviating efficacy on skin inflammation induced by UVB irradiation and application of Sq-OOH in hairless mice.