Objective:To study the effect of JAK/STAT signaling pathway on extracellular release of high mobility group box 1 (HMGB1) in endotoxin-induced hepatocytes. Methods:HMGB1 concentration was determined in the culture medium of 100 μg/L lipopolysaccharide-induced BRL-3A hepatocytes by enzyme-linked immunosorbent assay (ELISA),and the change of HMGB1 mRNA expression was detected by RT-PCR method. The effects of JAK/STAT pathway inhibitors (tyrphostin AG 490 and fludarabine) with various concentrations on HMGB1 mRNA expression and extracellular release were investigated. Results:The level of HMGB1 mRNA expression and HMGB1 concentration in the culture medium significantly increased after BRL-3A hepatocytes induced by lipopolysaccharide for 24 hours(P < 0.01). 25 μmol/L tyrphostin AG 490 and 50 μmol/L fludarabine partly inhibited HMGB1 mRNA expression and extracellular release in lipopolysaccharide-induced BRL-3A hepatocytes(P < 0.05). Conclusion:Lipopolysaccharide induces hepatocytes to release HMGB1,which is related to intracellular JAK/STAT signaling pathway.