Aim CXCL16 can be a potential player in atherogenesis.To investigate the effects of Fenofibrate on atherosclerosis and CXCL16 expression.Methods ApoE knockout mice were divided into two groups depending on treating with fenofibrate or distilled water.After 8 weeks all mice were euthanized,and ELISA was used to detect serum CXCL16 level.Aorta paraffin sections were performed with HE stain to observe and analyze atherosclerotic lesion.Expressions of CXCL16 and CXCR6 were detected by immunohistochemistry and analyzed by digital quantitative analysis software.Real-Time PCR was used to quantify CXCL16 mRNA expression.Results The atherosclerotic lesion and the expression of CXCL16 and CXCR6 were alleviated in fenofibrate group than that in control.CXCL16 mRNA expression was significantly decreased in Fenofibrate group.Conclusion Fenofibrate attenuated atherosclerosis and down-regulated CXCL16 protein and mRNA expression in ApoE knockout mice,which were independent of its cholesterol-lowering effect.