To investigate the regulatory effects of high glucose on the expression of Toll Like Receptor(TLR) Gene and the level of tumor necrosis factor(TNF)-α and interleukin(IL) -6 in human peripheral-blood mononuclear cells . Methods The alterations of TLR1～10 mRNA expression in human peripheral-blood mononuclear cells were quantitated using real-time quantitative-polymerasechain reaction. The level of TNF-α and IL-6 were measured by Enzyme-Linked Immuno Sorbent Assay . The anti-TLRmAb were used to block the mononuclear cells 30 min, high glucose was used to stimulate the cells. Rusults high glucose strongly up-regulated the expression of TLR3、5 mRNA but the expression of the other sub-TLRs weren’t changed .The concentrations of TNF-α、IL-6 were 86.40±8.46 and 874.66±92.84 in high glucose group, all significantly higher than that the control experiment (60.49±6.80 and 541.80±81.08 , all P<0.01), The anti-TLR3mAb and anti-TLR5mAb were used to block the mononuclear cells , The concentrations of TNF-α、IL-6 (72.41±8.52 and 700.59±84.88) were lower than that in the high glucose group, all P<0.05 . Conclusion high glucose may be endogenous ligand of TLRs and high glucose can regulate the release of inflammation cytokines from human peripheral-blood mononuclear cells through TLR signal way.