Objective: Atherosclerosis is a syndrome affecting arterial blood vessels. It is a chronic inflammatory process occurring in the walls of arteries, in large part due to the accumulation of inflammatory cells. The present study was conducted to determine the effect of nuclear factor-kappa B (NF-觀B) decoy oligodeoxynuclerotides (ODNs) in an atherosclerosis animal model. Methods and Results: The test mice received intraperitoneal injections of lipopolysaccharide (LPS, 2 mg/ml) three times a week to induce atherosclerotic change. The mice were also fed an atherogenic diet for 12 weeks. 10 mg of NF-觀B decoy ODNs were injected into the tail vein. The mice were sacrificed after 4 and 12 weeks of the experimental diet. Biochemical analysis was showed that NF-觀B decoy ODNs significantly reduced serum levels of total cholesterol (TC) and triglyceride (TG) in atherosclerotic mice. Treatment with NF-觀B decoy ODNs decreased pro-inflammatory cytokines, tumor necrosis factor (TNF)-慣 and interleukin (IL)-1棺 and proteins related with fibrosis, transforming growth factor (TGF)-棺1 and fibronectin, in the LPS/fat induced mice. In addition, the expressions of vascular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 were markedly decreased in the mice treated with NF-觀B decoy ODNs compared to the LPS/fat induced mice without decoy ODNs treatment. Conclusion: These data suggest that NF-觀B decoy ODNs may exert an inhibitory effect on the expression of pro-inflammatory cytokines and cell adhesion molecules in an atherosclerosis animal model.