Abstract: Objective To investigate the effects of trimetylamine oxide (TMAO) on the inflammatory response of human aortic endothelial cells and mouse abdominal aorta, and further explore the activation of NF-κb in the inflammatory response signaling pathway. Methods The human aortic endothelial cells were divided into control group and TMAO group. The cells were treated with TMAO. The cell survival rate was detected by CCK-8 method. The mRNA expression of inflammatory response factor was detected by real-time fluorescent quantitative PCR. The protein expression and its nuclear status was detected by western blotting, in vivo mice were divided into control group and TMAO group. Mice were treated with intraperitoneal injection of TMAO, and the expression of inflammatory factor mRNA was detected by real-time fluorescent quantitative PCR. Results At TMAO 1 000, 3 000, and 5 000 μmol/L, the survival rate of the cells was decreased (P<0.01). The mRNA expression of inflammatory response factors was significantly increased after TMAO treatment of cells and mice. High increased phosphorylation of p65 and p65 and proteins into the nucleus (P<0.05). Conclusions TMAO may stimulate vascular endothelial cells to release inflammatory response factors through activation of NF-κb signaling pathway, and may affect the occurrence and development of atherosclerosis.