Objective:To investigate whether high mobility group box chromosomal protein 1(HMGB1) can activate macrophages to secrete IL-18.Methods: Mouse peritoneal macrophages were cultured with HMGB1 for indicated period, then the mRNA and protein expression of IL-18 and IL-18 receptors were examined by real-time PCR, ELISA, and flow cytometric analysis. Toll-like receptor（TLR）2 and 4 agonists (1 μg/ml Pam3Cys or 100 ng/ml LPS) were used as parallel controls.Results: Two hours after culture with HMGB1(100 ng/ml), IL-18 mRNA expression was greatly increased. The expression of IL-18 protein was also greatly increased 24 h after culture with HMGB1, and the expression of IL-18R was slightly up-regulated. Pam3Cys (1 μg/ml) and LPS(100 ng/ml) could promote the expression of IL-18 at both mRNA and protein levels in the macrophages, and could up-regulate IL-18 receptors. Conclusion: HMGB1 can directly activate macrophages to secrete IL-18 and to express IL-18 receptor, suggesting that IL-18 may mediate the proinflammatory activity of HMGB1.