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Objectives. Percutaneous coronary intervention (PCI) is the mainstay treatment for coronary artery disease but complications such as in-stent restenosis and thrombosis remain problematic. Radiofrequency balloon angioplasty (RBA) can improve lumen dimension, fusing intimal tears, and artery dissection but is associated with higher restenosis rate. Methods. After establishing an atherosclerosis model based on endothelial abrasion and high cholesterol diet, forty-five rabbits were randomly divided into three groups: RBA (n=20), percutaneous transluminal angioplasty (PTA) (n=20), and control groups (n=5). The RBA and PTA groups were subdivided according to harvested time posttreatment, respectively (1 hour, 7 days, 14 days, and 28 days). Aorta segments were then isolated for hematoxylin and eosin staining, Masson trichrome staining, immunohistochemistry, and Western blot for TLR-4, NF-κB, MCP-1, and VCAM-1expression. Results. At 28 days, intimal area was significantly lower in the RBA group compared to the PTA and control groups, whilst luminal and medial area were comparable in the RBA and PTA group but higher and lower than the control group, respectively. Expression of TLR-4, NF-κB, MCP-1, and VCAM-1 showed no significant difference between RBA and PTA groups. Conclusions. RBA can depress the intimal hyperplasia and promote dilatation of the artery to greater extents than PTA at 28 days. However, this did not involve TLR-4 signaling pathway, which likely plays a negligible role in mediating restenosis. Reduction of intimal hyperplasia may be due to injury of ablation to the tunica media and inhibition of VSMC proliferation and migration. [ABSTRACT FROM AUTHOR]