Abstract: Objective To investigate protective effect of glycyrrhizic acid (GA) against lupus nephritis in MRL/lpr mice and explore its underlying mechanisms. Methods Forty MRL/lpr mice were randomized equally into blank control group, dexamethasone (1.5 mg/kg) group, GA (20 mg/kg) group, and GA (40 mg/kg) group with corresponding treatments for 7 days, with 10 wild-type mice as the control group. Serum levels of uric acid and creatinine and inflammatory cytokines in the serum and kidney were tested after the treatments using enzyme-linked immunosorbent assays (ELISA). The pathological changes in the kidneys were detected using HE staining, and the protein expressions of NLRP3, ASC, caspase-1, IL-1β, p-NF-κB, NF-κB, p-IκBα, and IκBα were detected with Western blotting. Results GA obviously decreased serum levels of uric acid and creatinine, decreased inflammatory cytokines in the serum and kidney, ameliorated renal pathologies and inhibited the expressions of NLRP3, ASC, caspase-1, IL-1β, p-NF-κB, and p-IκBα proteins in MRL/lpr mice. Conclusion GA has protective effects against lupus nephritis in MRL/lpr mice.