Objective:To investigate the role of Bmi-1 in preventing skin aging in mice. Methods:The phenotype of skin was compared between wild-type and Bmi-1 gene knock-out mice at 2 and 4 weeks of ages by histology, immunohistochemistry and Western-blot,respectively. Results:Bmi-1 gene knock-out mice displayed a premature aging phenotype in skin including thinner skin with hyperkeratosis of the epidermis, reduced collagen and subcutaneous fat deposition in skin matrix. Proliferating cell nuclear antigen immunopositive cells in skin were decreased significantly in Bmi-1 gene knock-out mice compared to their wild-type littermates. The expression of cell cycle dependent kinase inhibitive factors including p16,p19 and p27 was up-regulated markedly in skin from Bmi-1 gene knock-out mice. Conclusion:Bmi-1 plays an important role in preventing skin aging by inhibiting the expression of cell cycle dependent kinase inhibitive factors and stimulating cell proliferation.