Objective:To study the extracellular release of high mobility group box 1(HMGB1)in mast cells induced by lipopolysaccharide(LPS)and related intracellular signaling pathways. Methods:The changes of HMGB1 concentration in the culture medium and HMGB1 mRNA expression of P815 mast cells were investigated using enzyme-linked immunosorbent assay(ELISA)and RT-PCR method after stimulation with various concentrations of LPS. The effects of MAPKs pathway inhibitors(SB203580,SB202190,U0126 and PD98059)on extracellular release of HMGB1 were observed in LPS-induced mast cells. Results:LPS induced extracellular release of HMGB1 in mast cells in a dose- and time-dependent manner. The level of HMGB1 mRNA expression significantly was increased by stimulation with 100 μg/L LPS for 8,24 or 48 hours(P < 0.01). SB203580 and SB202190 partly inhibited HMGB1 release in LPS-induced mast cells(P < 0.05). But no effects were observed in U0126 and PD98059 treated group. Conclusion:LPS can induce mast cells to release HMGB1,in which the intracellular p38 MAPK signaling pathway is involved.