Aim To investigate the effects of licochalcone A(Lico A)on the expression of inflammatory cytokines in macrophages of human acute monocytic leukemia cell line (THP-1) induced by lipopolysaccharide (LPS) in vitro. Methods 100 μg /L phorbol ester (PMA) was used to induce THP-1 cells for 48 hours, after the differentiation of THP-1 cells, which became macrophage, and cells were divided into control group, LPS group and LPS combined with concentration (20, 0,5 mg/L) of Lico A. The levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. The levels of Toll like receptor-4(TLR-4) and nuclear factor kappa B (NF-κB) mRNAs were tested by real-time PCR. The levels of TLR-4, NF-κB,Iü kappa B kinase alpha (IKKα), phosphorylated IKB-alpha (p-IKB-α), cyclooxygenase-2 (COX-2) and isoform of nitric oxide synthase (iNOS) proteins were examined by Western blot. Results The expression levels of TNF-α, IL-1 and IL-6 were up-regulated in the v macrophages after stimulated by LPS, Lico A could reduce the elevated expression levels of TNF-α, IL-1 and IL-6 induced by LPS. The expression of TLR-4 significantly increased after stimulated by LPS and NF-κB was activated. Lico A could reverse the above changes and prevent the activation of NF-κB. Conclusion Lico A could inhibit LPS-induced inflammatory response in THP-1 macrophages via TLR-4 /NF-κB pathway.