Background: The effects of radiation on tissues vary depending on the radiation type. In this study, a minipig model was used to compare the effects of β-rays from 166 Ho and γ-rays from 60 Co on the skin. Materials and Methods: In this study, the detrimental effects of βand γ-irradiation on the skin were assessed in minipigs. The histopathological changes in the skin from 1 to 12 weeks after exposure to 50 Gy of either β-(using 166 Ho patches) or γ-(using 60 Co) irradiation were assessed. Results and Discussion: The skin irradiated by β-rays was shown to exhibit more severe skin injury than that irradiated by γ-rays at 1-3 weeks post-exposure; however, while the skin lesions caused by β-rays recovered after 8 weeks, the γ-irradiated skin lesions were not repaired after this time. The observed histopathological changes corresponded with gross appearance scores. Seven days post-irradiation, apoptotic cells in the basal layer were detected more frequently in β-irradiated skin than in γ-irradiated skin. The basal cell density and skin thickness gradually decreased until 4 weeks after γand βirradiation. In β-irradiated skin lesions, and the density and thickness increased sharply back to control levels by 6-9 weeks. However, this was not the case in γ-irradiated skin lesions. In γ-irradiated skin, cyclooxygenase-2 (COX-2) was shown to be expressed in the epidermis, endothelial cells of vessels, and fibroblasts, while β-irradiated lesions exhibited COX-2 expression that was mostly limited to the epidermis. Conclusion: In this study, β-rays were shown to induce more severe skin injury than γ-rays; however, the β-rays-induced injury was largely repaired over time, while the γ-rays-induced injury was not repaired and instead progressed to necrosis. These findings reveal the differential effects of γand β-irradiation on skin and demonstrate the use of minipigs as a beneficial experimental model for studying irradiation-induced skin damage.