Aim To explore the role and mechanism of liver X receptor α(LXRα)agonist on increased cleaved interleukin-1β(IL-1β)expression caused by Nod-like receptor protein-3(NLRP3)inflammasome in macrophages. Methods THP-1 cells were activated into macrophages by phorbol 12-myristate 13-acetate(PMA）, and then were divided into different groups: model group(1 μg/L cholesterol crystal）, GW3965 high, middle and low concentration groups(added 30 μmol/L, 10 μmol/L, 3.3 μmol/L GW3965 based on model group）, GW3965＋GGPP group(10 μmol/L GW3965 plus 10 μmol/L GGPP）, GGPP group(10 μmol/L GGPP）, ABCA1 antibody and apolipoprotein E(ApoE)antibody groups(10 μmol/L GW3965 plus 1∶200 ABCA1 or ApoE respectively）. Total RNA, total protein, nuclear protein and supernatant protein were extracted after 48 h treatment. mRNA levels of ABCA1, NLRP3, Caspase-1 and IL-1β were detected by real-time PCR, and the protein levels of ABCA1, NLRP3, Caspase-1, nuclear NF-κB p65, IL-1β and cleaved IL-1β were measured by Western blot. Results Compared with control group, cleaved IL-1β, NLRP3 and Caspase-1 levels were significantly increased after the stimulation of cholesterol crystal(P<0.05)in model group. The treatments of middle and high concentration GW3965 attenuated the alterations(P<0.05）. Compared with GW3965 middle concentration group, there were significant statics differences of the above biomarker levels in GW3965＋GGPP group, but not in ABCA1 antibody or ApoE antibody group. Conclusion LXRα agonist GW3965 can attenuate the increased level of cleaved IL-1β caused by NLRP3 Inflammasome, and NF-κB p65 pathway may be involved in the mechanism.