Based on the SAR analysis of glycyrrhizin, 18α-glycyrrhetinic acid monoglucuronide (18α-GAMG) with strong inhibition against LPS-induced NO and IL-6 production in RAW264.7 cells was discovered. Western blotting and immunofluorescence results showed that 18α-GAMG reduced the expression of iNOS, COX-2, and MAPKs, as well as activation of NF-κB in the LPS-stimulated RAW264.7 cells. Further <i>in vivo</i> results showed that 18α-GAMG could significantly improve the pathological changes of CCl<sub>4</sub>-induced hepatic fibrosis.