Objective To investigate the relationship between the thrombospondin-1 (TSP-1) and carotid atherosclerosis and its related indicators in patients with type 2 diabetes mellitus (T2DM). Methods A total of 101 T2DM patients were divided into T2DM group (A group, n=52) and T2DM with carotid artery atherosclerosis group (B group, n=49) according to whether complicated with carotid artery atherosclerosis, and 50 normal healthy persons were used as the normal group (C group , n=50). The TSP-1 and other clinical indicators were detected including fasting blood sugar (FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fibrinogen (Fib) and homocysteine (homocysteine). The differences between TSP-1 and other related indicators were analyzed. Results There were no significant differences in diastolic blood pressure (DBP) and body mass index (BMI) between the 3 groups (P>0.05). The level of systolic blood pressure (SBP) was significantly higher in group B than that of group A and group C (P<0.01), but there was no significant difference between group A and group C (P>0.05). There were no significant differences in TC, TG and HDL-C between three groups (P>0.05). The values of TSP-1 and Hcy were increased sequentially in group B, group A and group C (P <0.05). There were significant differences in FPG, HbA1c, Fib, FINS and LDL-C between three groups (P<0.05). TSP-1 was positively correlated with FPG, FINS, HbA1c, Fib and Hcy (r= 0.585, 0.341, 0.701, 0.409 and 0.351, P < 0.05). Linear regression analysis showed that TSP-1 was affected by FINS, HbA1c and Fib, and HbA1c was more important. Conclusion TSP-1 is associated with the occurrence and development of diabetic macrovascular complications. It has good clinical value for early detection, early treatment and delaying the progress of diabetic macrovascular diseases.