Aim T0901317 is a synthetic liver X receptor (LXR) agonist. This study was to investigate the effects and potential mechanisms of T0901317 on proinflammatory cytokine release from lipopolysaccharide (LPS)-induced THP-1 macrophages. Methods Human THP-1 macrophages were induced using phorbol-12-myristate acetate (PMA, 160 nmol/L) for 24 h, then cells were divided into four groups: control group, LPS group, T0901317 group and LPS＋T0901317 group. Secretion of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) was performed by enzyme-linked immunosorbent assay (ELISA). The siRNAs for ATP-binding cassette transporter A1 (ABCA1) were transfected into THP-1 macrophages by positive ion liposome Lipofectamine^TM2000. The mRNA expression of ABCA1, ABCG1 and Toll like receptor 4 (TLR4) were examined by real-time PCR analysis. The proteins expression of ABCA1, ABCG1, TLR4 and nuclear factor-κB (NF-κB) p65 were examined by Western blot. Results T0901317 inhibited the release of TNF-α, IL-6 and IL-1β induced by LPS, and promoted the expression of ABCA1 and ABCG1 on THP-1 macrophages. Transfection of ABCA1 siRNA significantly decreased the of expression ABCA1 protein and weakened the effect of T0901317 on the LPS-stimulated inflammatory response. Furthermore, T0901317 repressed the expression of TLR4 and the translocation of NF-κB to the nucleus. Conclusions T0901317 inhibited the release of inflammatory cytokine that induced by LPS, and the mechanisms may be related to promotion of membrane transporter ABCA1 expression and inhibition of membrane receptors TLR4 and the transcription factor NF-κB expression.