Aim To explore the effect of fenofibrate on oxidized low density lipoprotein (ox-LDL) uptake in adipocytes from hypercholesterolemia rabbits and the expression of CD36. Methods 10 male New Zealand white rabbits were fed with 1% cholesterol, 7.5% protein, 8% lard diet for 8 weeks, and were randomly divided into two groups: ① high cholesterol group: maintained cholesterol diet for 4 weeks; ② treatment group: the same cholesterol diet supplemented with fenofibrate (30 mg/kg/day) for 4 weeks. And control group was fed with normal diet for 12 weeks. Subcutaneous adipose tissues were collected for adipocytes culture. CD36 and PPARγ mRNA expression were evaluated by RT-PCR. Results The specific cell association and degradation of 125 Ⅰ ox-LDL in adipocytes from the three groups exhibited a dose-dependent saturation pattern. The endocytic uptake and degradation of 125 Ⅰ ox-LDL in adipocytes from high-cholesterol groups were inhibited; fenofibrate treatment enhanced the 125 Ⅰ ox-LDL uptake and degradation in adipocytes from hypercholesterolemia rabbits. There were obviously difference among the three groups (p<0.05). The expression of PPARγ and CD36 mRNA in adipocytes were down-regulated in high cholesterol group and the CD36 mRNA expression in adipocytes of treatment group was similar to the control group. Conclusion Fenofibrate treatment improved the ox-LDL uptake and degradation in adipocytes from hypercholesterolemia rabbits and up-regulated CD36 mRNA expression in adipocytes.