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Introduction Glycyrrhiza glabra is a plant used in traditional medicine across the world for its pharmacological value. Its value has been proved such as anti-cough, anti-diabetes, anti-microbial and antioxidant effects. Materials and Methods In this study the effect of a glycyrrhizin component of HMGB1's microglia product becomes in the survey, at terms of informative mediating on in vitro modeling that have six groups (with three replications). In negative control group no Gly and LPS was involved. In positive control group, the cells were  induced with LPS and no Gly, and in 3, 4, 5 and 6 groups 0.2, 0.4, 1.2 and 4 µg/ml Gly were added respectively. The amounts of HMGB1 were measured at 24, 48 and 72 hours with the sandwich ELISA kit.  Results At all three times, the HMGB1 were decreased with increasing Gly, but in 24 h between 0.2 and 1.2 concentrations and in 72 h between positive control and 0.2 no significant difference were found. So it is concluded that this amount should be increased for the effective dose. Conclusion Along with previous studies, Glycyrrhizin reduced the production of HMGB1 in the microglial cell line.