Objective To investigate whether P12，a kind of lipopolysaccharide（LPS）-binding protein（LBP） inhibitory peptide，could suppress the binding of LPS to alveolar macrophages（AMs） in a mouse model of endotoxemia in vivo.Methods Forty mice were randomly divided into five groups，ie.a control group，an endotoxemia group，a low dose P12-treated group，a middle dose P12-treated group and a high dose P12-treated group.Mouse model of endotoxemia was established by LPS injection intraperitoneally in the endotoxemia group and P12-treated groups.P12 was instilled via the tail vein.The effects of P12 on the binding of LPS to AMs were determined by flow cytometric analysis and quantization by mean fluorescence intensity(MFI).The productions of tumor necrosis factor α(TNF-α) in serum of mice were measured by enzyme-linked immunosorbent assay(ELISA).Results MFI in AMs from low，middle and high dose P12-treated groups was 40.08%，30.76% and 24.45%，respectively，which was higher than that of the control group(4.61%)，but less than that of the endotoxemic mice(45.31%).The concentration of TNF-α in serum of low，media and high dose P12-treated mice was (112.69±19.78)pg/mL，(86.34±9.25) pg/mL，(70.48±8.48)pg/mL respectively，which was higher than that of the control group[(24.88±5.82)pg/mL]，but less than that of the endotoxemic mice[(180.17±39.14)pg/mL].Conclusion The results suggest that P12 inhibit the binding of LPS and AMs，thus reduce the proudction of TNF-α stimulated by LPS.