The decreased production of antimicrobial peptides in tissues surrounding the burn sites has been described in patients with severe burn injury. Small numbers of Pseudomonas aeruginosa spread easily to the whole body of burn mice when infected at burn site tissues. Gr-1(+)CD11b(+) cells, demonstrated in tissues surrounding the burn site, are inhibitory on the production of antimicrobial peptides by EK. In this paper, the decreased production of antimicrobial peptides by EK influenced by Gr-1(+)CD11b(+) cells was shown to be restored by glycyrrhizin. CCL2 and IL-10 were determined to be effector soluble factors for the suppressor activities of Gr-1(+)CD11b(+) cells on antimicrobial peptide production by EK. However, Gr-1(+)CD11b(+) cells, which were treated previously with glycyrrhizin, did not produce these soluble factors. Also, sepsis stemming from P. aeruginosa burn-site infection was not demonstrated in burn mice treated with glycyrrhizin. These results suggest that through the improved production of antimicrobial peptides in tissues surrounding the burn area, sepsis stemming from P. aeruginosa wound infection is controllable by glycyrrhizin in severely burned mice.