Abstract: 【Abstract】 Objective To investigate whether serum cystatin C (Cys C) concentration correlates with the severity of carotid atherosclerosis (CAS) in patients with type 2 diabetes mellitus (DM). Methods This study enrolled 633 type 2 DM patients met the inclusion/exclusion criteria. All the patients were subjected to the measurement of serum Cys C, concentration, complete blood count, and blood biochemical test. The severity of CAS was evaluated by Doppler ultrasound to define intimal medial thickness (IMT) of carotid artery, the location and size of atherosclerotic plaque. Based on the estimated glomerular filtation rate (eGFR), the patients were divided into DM with chronic kidney diease (CKD) group (DM-CKD) and DM without CKD group (DM-NCKD), then were further divided into two subgroups by IMT and AS plaque. The relationship of serum Cys C with the severity of CAS was evaluated by the comparison between the two groups, correlation analysis and multiple linear regression analysis. Results In 396 DM-NCKD patients with the eGFR ≥60 mL/(min·1.73 m2), Cys C concentration of IMT thickening group was higher than that of normal IMT group 〔(1.00±0.20) mg/L vs. (0.90±0.30) mg/L, P<0.05〕, but the difference was not statistically significant after the adjustment for confounding factors. The patients with obvious CAS plaques formation had higher Cys C concentration than those without AS plaques formation 〔(1.05±0.27) mg/L vs. (0.89±0.22) mg/L, P<0.05〕. Moreover, the concentration of Cys C was correlated with the severity of CAS (r=0.338, P<0.001), even after the adjustment for confounding factors (r=0.14，P=0.005). Multiple linear regression analysis also showed a close correlation of Cys C with the severity of CAS (B=0.071，P=0.001). Analysis of variance showed that the severity of CAS was increased accordingly with the increasing level of Cys C. However, the concentration of Cys C was not correlated with the severity of CAS in 237 DM-CKD patients. Conclusion The concentration of Cys C was positively correlated with the severity of CAS, it may be a candidate marker of CAS severity in type 2 DM patients without CKD.