Chronic inflammation plays a pivotal role in atherogenesis. Antioxidants have a potential role in the prevention and treatment of atherosclerosis. The effects of palm oil-derived tocotrienol-rich fraction (TRF) supplementation on inflammation are not well established. This study aims to investigate the effects of TRF supplementation on the inflammatory biomarkers and adhesion molecules in severe atherosclerosis. A total of 28 New Zealand white rabbits were given 1% high-cholesterol diet (HCD) for five months and randomised from the second month onwards into one of five intervention groups: Placebo, TRF 15, 30, 60 and 90 mg/kg/day. Treatment was given for three months and the animals were fed HCD throughout the duration. At the end of the study, the aortas were obtained, stained with Sudan IV, fixed in formalin, embedded in paraffin and immunostained for tissue intracellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), E-selectin, smooth muscle actin (SMA), and nuclear factor-κB (NF-κB). The amount of atherosclerotic lesions was not significantly different between the groups and compared to placebo. Qualitative analysis showed lower trend of ICAM-1, IL-6, E-selectin and NF-κB but higher trend of SMA tissue expression in TRF-treated groups especially at low dose of TRF (TRF-15) compared to placebo. Quantitative analysis showed lower ICAM-1 and E-select in positivity in TRF-15 compared to placebo group (25.1 ± 7.4 % vs. 3.8 ± 2.0 %, 23.2 ±6.5 % vs. 4.2± 2.1 %, respectively, p<0.05). In conclusion, low dose TRF is potentially beneficial in attenuating vascular endothelial activation in severe atherosclerosis.