To investigate the alleviative effects of Cnidium officinale water extract (COWE) on inflammation and skin barrier damage, both the irradiation of UVB and the application of squalene monohydroperoxide (Sq-OOH) to the backs of hairless mice were performed for 4 weeks. And at the same time experimental materials were applied topically. The skin erythema indices for the positive control (PC, 0.01% retinoic acid) and experimental (E, COWE) groups were lower than that of the control (C) group. Whereas both the lipid and water capacities for the PC and E groups were higher than those of the C group. Epidermis and dermis of the C group were remarkably thickened in comparison with the PC and E groups. Relatively much less number of inflammatory cells, including lymphocytes and neutrophils were found in dermis of the PC and E groups compared with the C group. Lipid lamellae of the C group were broken severely, showing an irregular arrangement and lipid content was much reduced. Whereas those of the PC and E groups were almost intact with a regular arrangement, that were similar to that of the N group. Taken the results all together, it was confirmed that COWE could be effective natural herbal material for the alleviation of inflammation and skin barrier damage in hairless mice skin that were induced by UVB irradiation and Sq-OOH application.