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Objective: CX3CL1 played an important role in atherosclerosis recently. We investigated the association between the chemokine CX3CL1 with coronary artery disease in type 2 diabetes mellitus. Methods: CX3CL1 expression in carotid artery specimens was analysed by immunohistochemistry. The study was conducted in 400 coronary artery disease in type 2 diabetes mellitus and 400 control subjects in a case-control study. CX3CL1 gene rs170364 variant was detected by the directing sequencing technology. Results: CX3CL1 expressions were increased markedly in carotid artery plaque than in normal carotid artery. CX3CL1 gene rs170364 genotype (GG, GT and TT) frequency in coronary artery disease in type 2 diabetes mellitus is 42.7%, 40.0% and 17.2%, and 50.2%, 39.6% and 10.2% in the control group. CX3CL1 gene rs170364 variant is a genetic risk factor for coronary artery disease in type 2 diabetes mellitus (P <0.05). Logistic regression analysis with adjustments for other risk factors showed that the CX3CL1 gene rs170364 T allele significantly increases the risk of coronary artery disease in type 2 diabetes mellitus compared with the control subjects (P <0.05). Conclusion: Our study shows that the CX3CL1 expression increased in the carotid plaques and serum of the coronary artery disease in type 2 diabetes mellitus. CX3CL1 gene rs170364 variant may be considered a genetic risk factor for coronary artery disease in type 2diabetes mellitus. [ABSTRACT FROM AUTHOR]