Objective To investigate the effects of AGE-LDL in murine bone marrow-derived mast cells degranulation and relative signal pathways.Method Bone marrow-derived cells were harvested from male, 6-8 weeks old C57/BL6 and TLR4-/-mice, then cultured in medium supplemented with rmIL-3 and rmSCF.Mast cell purity was examined in 4-6 weeks by toluidin blue staining and flow cytometry.Degranulation of MCs, stimulated by different doses of AGE-LDL, was quantified by assaying release of histamine and secretion of beta-hexoaminidase.Expressions of a receptor for AGE-LDL and TLR4 were assessed by real-time PCR, flow cytometry and western blot.Potential involved signal pathways were assessed by detecting expression of NF-kappaB, p38 MAPK, Erk1/2 and JNK phosphorylation with western blot and relative signal pathway inhibitors.Results AGE-LDL dose-dependently induced release of histamine and secretion of beta-hexoaminidase within 30min coincidence with increased expression of TLR4, which were remarkably reduced in BMMCs from TLR4 knockout mice.AGE-LDL could increase phosphorylation of p38, ERK1/2 kinases and NF-kappaB, but not JNK, in BMMCs from WT mice, which were absent in TLR4-/-mast cells.p38MAPK, ERK1/2 and NF-kappaB inhibitors could reduce the pathological effects of AGE-LDL in mast cells.Conclusion Data from our study confirmed that AGE-LDL could activate mast cell degranulation via TLR4-mediated signal pathway, which might partly explain increased risk of acute cardiovascular events in diabetes.