Background: E. senticosus extract (ESE) has been used as an antiaging agent in the skin although it has several systemic beneficial effects. Objectives: The effects of E. senticosus extract (ESE) and its active ingredient phlorizin (PZ) were investigated. Methods: Cultured normal human keratinocytes and skin equivalents are used to test the effects of PZ whether they affect proliferative activity of keratinocytes and how they regulate these effects. Results: The epidermis became slightly thickened on addition of 0.002% ESE. The staining intensity of p63 and proliferating cell nuclear antigen (PCNA) is increased, and integrin メ6 was up-regulated. Analysis of ESE by HPLC and NMR spectroscopy confirmed that PZ is the main ingredient. SE models were treated with PZ and the staining intensity of p63 and PCNA is also increased. Expression of integrin メ6, integrin モ1, and type IV collagen was also increased. Next, levels of miR135b and mRNA levels of integrin メ6, integrin モ1, and type IV collagen were examined in cultured normal human keratinocytes. Levels of mRNA for type IV collagen were increased and levels of miR135b were down-regulated. Conclusion: PZ can affect the proliferative potential of epidermal cells in part by microenvironment changes via miR135b down-regulation and following increased expression of type IV collagen.