Abstract The root of Glycyrrhiza glabra (licorice) and its principle component (glycyrrhizin) have revealed various immunomodulatory properties that fight off attacking pathogens. In our previous studies, glycyrrhizin was shown to prevent infectious complications developed in mice with systemic inflammatory response syndrome (SIRS) through the inhibition of CCL2 production by PMN-II. c-fos (one of the nuclear transcription factors) is known as a CCL2 gene promoter. Therefore, in the present study, c-fos mRNA expression in PMN-II treated with or without glycyrrhizin was analyzed. For these studies, SIRS was induced by a flame burn injury (3rd degree, 25% TBSA burns). PMN-II were isolated from the peripheral blood of mice 18 hrs after burn injury by Ficoll-Hypague and dextran sedimentations, followed by the depletion of contaminating monocytes using magnetic beads coated with anti-F4/80 mAb. In the presence of Staphylococcus aureus antigen (0.0075%), PMN-II (1 x 106 cells/ml) were cultured with various doses of glycyrrhizin for 12 hrs, and the culture fluids obtained were assayed for CCL2. Also, the obtained cells were analyzed for c-fos mRNA by RT-PCR. In the results, 3.7 ng/ml of CCL2 was detected in the culture fluids of PMN-II, while PMN-II treated with glycyrrhizin did not produce CCL2. c-fos mRNA was expressed in PMN-II, but not in PMN from normal mice. When PMN-II were treated with 10 μg/ml of glycyrrhizin, c-fos mRNA expression was greatly decreased. These results suggest that c-fos expression in PMN-II may be controlled by glycyrrhizin when CCL2 production by these PMN is inhibited by the compound. This study was supported by SHC NA #8840.