[Abstract] Objective To investigate the therapeutic effect of licorice zinc on melasma. Methods Melasma was induced by 100 mJ/cm2 UVB irradiation combined with 15 mg/kg progesterone injection. Tranexamic acid (0.065 g/kg) and low (0.65 g/kg)/medium (1.3 g/kg)/high (2.6 g/kg) zinc licorice were treated for 14 days. Skin was taken for HE and Masson-Fontana staining; and SOD, MDA, GSP-Px, TNF-α, IL-1β and IL-6 contents; plasma protein Nrf-2, nuclear protein Nrf-2, and HO-1 expression levels were measured. Results High dose of zinc licorice significantly reduced melanocyte formation, collagen cell necrosis and inflammatory infiltration, significantly up-regulated the expression of GSP-Px and SOD, decreased the expression of MDA, IL-6, IL-1β and TNF-α, up-regulated the expression of nuclear proteins Nrf-2 and HO-1, and down-regulated the expression of plasma protein Nrf-2. Conclusion Zinc licorice activates Nrf-2/HO-1 pathway to initiate high expression of HO-1, SOD and GSP-Px against oxidative stress, thereby reducing melanogenesis.