Background: Adiponectin had been nominated as a positive factor on functional recovery for its virtue against energy metabolism related regulation especially with AMP-activated protein kinase (AMPK) and SIRT1. But there are few reports related with skin or keratinocytes. Objectives: We aim to recover the possibility of adiponectin as a promising anti-aging agent and supplement for antimicrobial barrier. Methods: Adiponectin had been treated to normal or premature senescent keratinocytes. SA モ-galactosidase stain and assay, AMPK-SIRT1-FoxOs and MAPK/NFリB signal transduction pathway were evaluated by immunoblot, SIRT1 activity assay and RT-PCR. Results: The adiponectin stimulation reduced premature senescence and restituted human モ-defensin 2 and LL-37 in aged skin. Adiponectin upregulated and recovered AMPK activity in senescent keratinocyte and up-regulated SIRT1 activity suppressed NFリB p65. Conclusion: These evidences suggest the positive possibilities of anti-aging agent and improved skin immune barrier through adiponectin stimulation related signal transduction.