Objective: To study the relationship between serum levels of insulin-like growth factor-1 (IGF-1), cystation-C (Cys-C), interleukin-6 (IL-6) and atherosclerosis in middle and old age patient with newly diagnosed type 2 diabetes mellitus (T2DM). Methods: A total of 206 patients with newly diagnosed T2DM at the age of (67.3±10.4) years were enrolled. Based on color Doppler ultrasound examination, the patients were divided into 2 groups: Control group, the patient without carotid plaque or increased intima thickening, n=105 and Experiment group, patient with carotid plaque or increased intima thickening, n=101. The general information, fasting blood glucose, 2h postprandial blood glucose, glycosylated hemoglobin, LDL-C, HDL-C, TG, TC and IGF-1, Cys-C, IL-6, hs-CRP were recorded and compared between 2 groups, BMI was calculated in all patients. Results: Compared with Control group, Experiment group had increased carotid intima-media thickness (CIMT), elevated serum levels of Cys-C, IL-6, hs-CRP and reduced IGF-1, allP<0.05. Multiple Logistic regression analysis showed that CIMT was negatively related to IGF-1 (r=-0.493,P<0.01), positively related to Cys-C, IL-6 and hs-CRP (r=0.464,r=0.219 andr=0.618, allP<0.01). Conclusion: Serum levels of Cys-C and IL-6 might be the independent risk factors for atherosclerosis occurrence in meddle and old patients with T2DM; combined detection of IGF-1, Cys-C and IL-6 could help clinical diagnosis in relevant patients.