Background: Although the topical application of glycolic acid (GA) could possibly exert some effects on the normal epidermal permeability function, the exact effects and its mechanism of action have not been well documented. Objective: This study was conducted to investigate the effects of GA on the expression of epidermal cytokines and to clarify its chelation effect on the epidermal calcium ions, which are known to control the secretion of lamellar bodies. Methods: After topical application of 70％ GA aqueous solution on the flank of hairless mice, the expression of epidermal IL-1α and TNF-α was assessed and the change of epidermal calcium ions was evaluated. Results: The results could be summarized as the following: ⑴ real time reverse transcriptase polymerase chain reaction and immunohistochemical staining studies showed increases in mRNA and protein expression of epidermal IL-1α: ⑵ the GA reduced intracellular calcium ion concentrations in vitro and resulted in the loss of epidermal calcium gradient in vivo. Conclusion: These results suggest that, like iontophoresis or sonophoresis, GA could influence the skin`s barrier homeostasis, possibly by lowering the epidermal calcium ions. (Korean J Dermatol 2004;42(3):290~299)