Background: Solar ultraviolet (UV) irradiation, in particular UVB with a wavelength range between 290 and 320 nm, induces different hazardous effects on the skin, including sunburn, photoaging and cancer. Protection against sun-induced damage is therefore a highly desirable goal. Chemoprevention is being investigated as a potential approach for the management of UV damages including skin cancer. Aim: In this study, to determine the relevance of our in vitro findings to in vivo situations, we assessed the effects of baicalin on UVB-mediated damages in mice skin. Methods: Balb/C hairless mice were topically pretreated (24 h before UVB) or post-treated (5 min after UVB) with baicalin (1 mg/cm2 skin area/mouse/100 l acetone) and were exposed to UVB 24 h later (180 mJ/cm2). The animals were sacrificed 1 and 24 h after the UVB exposure. Skin edema, histopathology changes, hydrogen peroxide (H2O2) and cyclobutane pyrimidine dimers (CPDs)-positive cells were assessed to determine the UVB-induced photodamage. Results: Our data demonstrated that a topical application of baicalin, either as a pretreatment or as a post-treatment, resulted in a significant decrease in UVB mediated increases in skin edema, skin hyperplasia and infiltration of leukocytes. Further, baicalin treatments (pre and post) also resulted in a significant decrease in UVB mediated (1) generation of H2O2 and (2) formation of DNA photolesions: CPDs. Conclusion: Based on these data, we suggest that baicalin could be developed as an agent for the management of conditions elicited by UV exposure including skin cancer.