Objective To investigate the therapeutic effect of licorice zinc on melasma. Methods Thirty-six BALB/ c mice were equally divided into blank group, model group, licorzinc low-dose group, licorzinc medium-dose group, licorzinc high-dose group and tranexamic acid group. Melasma was induced by 100 mJ/ cm2 UVB irradiation combined with 15 mg/ kg progesterone injection. Mice were treated with tranexamic acid (0. 065 g/ kg) and low (0. 65 g/ kg), medium(1. 3 g/ kg), or high (2. 6 g/ kg) doses of zinc licorice for 14 days. Skin was taken for HE and Masson-Fontana staining and measurement of SOD, MDA, GSP-Px, TNF-α, IL-1β, IL-6, plasma protein Nrf-2, nuclear protein Nrf-2 and HO-1 expression levels. Results Compared with model group, high-dose licorice zinc group showed decreased melanocyte formation, collagen cell necrosis, and inflammatory infiltration (P< 0. 01); decreased MDA, IL-6, IL-1β, TNF-α and plasma protein Nrf-2 expression (P< 0. 01); and increased GSP-Px, SOD and nuclear protein Nrf-2 and HO-1 expression (P< 0. 01). Conclusions Zinc licorice activates the Nrf-2/ HO-1 pathway to initiate high expression of HO-1, SOD and GSP-Px and fight oxidative stress, thereby reducing melanogenesis.