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Objective: To explore the regulating effects of cefodizime on cytokines expression of neutrophil response to Klebsiella pneumoniae (Kle. p) treatment. Methods: We detected the types and expression of cytokines secreted by neutrophils by cDNA array and RT-PCR. We also analyzed the changes of signal transduction in this process by detecting the expression of toll like receptor 4 (TLR4) and the inhibitor factor of κBα(Ⅰ-κBα) expressed by neutrophils. The activity of NF-κB DNA-binding in neutrophils was measured by electrophoretic mobility shift assay (EMSA). Results: Cefodizime increased the neutrophils production of TNF-α, IL-β and the mRNA expression of TLR4 in the early stage of Kle. p stimulation in mice, which seemed corresponding to the enhanced NF-κB DNA-binding activity. Conclusion: Cefodizime regulates the cytokines expression of neutrophils through the LPS-TLR4-NF-κB pathway by affecting the expression of TLR4 mRNA and the DNA binding activities of NF-κB in mice with the challenge of Kle. p.