Objective:To investigate the mechanism of 1,25(OH)2D3 in preventing skin aging. Methods:The phenotype of skin was compared between wild-type mice and 1α-hydroxylase gene knock-out littermates at 10 weeks of ages by histology,immunohistochemistry,western-blot and biochemical analysises,respectively. Results:1α-hydroxylase gene knock-out mice displayed a premature aging phenotype in skin including thinner skin with increased senescence associated β-galactosidase activity,flattening of the dermal-epidermal junction,reduced subcutaneous fat deposition and hair follicles number. Proliferating cell nuclear antigen(PCNA) immunopositive cells in skin were decreased, but terminal deoxynucleotidyl transferase dUTP nick end labeling positive areas were increased significantly in 1α-hydroxylase gene knock-out mice compared to their wild-type littermates. The expression of p16,p27,p53,NF--资B,active caspase-3 was up-regulated markedly in skin from 1α-hydroxylase gene knock-out mice. Reactive oxygen species and malondialdehyde levels were raised,whereas activities of superoxide dismutase and glutathione peroxidase were reduced in 1α-hydroxylase gene knock-out mice. Conclusion:1,25(OH)2D3 plays an important role in preventing skin aging by stimulating cell proliferation,inhibiting cells apoptosis and reducing oxidative stress.