AIM To investigate the effect of tocotrienol rich fraction of palm oil (TRF) on glucose metabolism in atherosclerotic mice and the possible mechanism. METHODS Apolipoprotein E gene deficient(ApoE~(-/-)) mice were divided into 3 groups as model control, TRF 0.05% and 0.2%(W/W) groups. 10% (W/W) fat and 0.2% (W/W) cholesterol were added into the diets to induce atherosclerosis formation. Oral glucose tolerance test and insulin tolerance test were conducted after mice were treated by TRF for 12 and 14 weeks respectively. Serum cholesterol, triglyceride, free fatty acid, and insulin levels were measured using corresponding kits. The mRNA expression levels for peroxisome proliferator-activated receptor γ(PPARγ), adiponectin and glucose transporter 4 (Glut4) in white adipose tissue (WAT) were determined by using quantitative real-time PCR. Activation of PPARγ by TRF was tested using luciferase reporter assays. RESULTS Compared with the model control group, TRF decreased non-fasting or fasting blood glucose levels and improved insulin sensitivity of ApoE~(-/-) mice. Both TRF groups showed decreased levels of triglyceride and free fatty acid. The mRNA level of adiponectin in WAT was up-regulated by (1.73±0.32) times in TRF 0.2% group compared with the control group. Glut4 mRNA level was increased (1.89±0.24) and (2.01±0.61) times compared with control group in TRF 0.05% group and TRF 0.2% group respectively. The fold inductions of TRF on PPARγ-ligand-binding domain, PPARγ1 and PPARγ2 activities were (2.7±0.2), (6.1±0.65) and (5.3±0.1) times compared with DMSO by using luciferase reporter assay. CONCLUSION TRF can improve glucose metabolism in atherosclerotic mice and this effect may be partly due to modulating the activity of PPARγ.