Aim To explore the relationship between serum Sclerostin, Endocan and type 2 diabetes mellitus (T2DM) subclinical atherosclerosis (SAS). Methods 117 cases of T2DM patients who were admitted to Chenzhou First People's Hospital from February 2019 to March 2021 were selected as the research objects, and the occurrence of SAS in T2DM patients was counted. The correlation between serum Sclerostin, Endocan and common carotid artery intima-media thickness (CIMT) were analyzed. The influencing factors of SAS in T2DM patients were analyzed. The value of serum Sclerostin and Endocan in predicting the occurrence of SAS in T2DM patients was analyzed. Results 68 cases (58.12%) developed SAS among the 117 cases of T2DM patients. The results of univariate analysis showed that the occurrence of SAS in T2DM patients was related to age, course of T2DM, complicated with hypertension, fasting plasma glucose(FPG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), fibrinogen, CIMT, Sclerostin and Endocan (P＜0.05). The results of multivariate Logistic regression analysis showed that age, LDLC, CIMT, FPG, Sclerostin and Endocan were all influencing factors for the occurrence of SAS in T2DM patients (P＜0.05). The results of Pearson correlation analysis showed that Sclerostin and Endocan were positively correlated with CIMT (P＜0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of serum Sclerostin, Endocan and their combination in predicting the occurrence of SAS in T2DM patients were 0.771 (95%CI: 0.616～0.926), 0.712 (95%CI: 0.493～0.929) and 0.827 (95%CI: 0.657～0.988), respectively. Conclusions T2DM patients have a higher risk of developing SAS. Serum Sclerostin and Endocan are related to the occurrence of SAS in T2DM patients. The combination of the two has a high efficiency in predicting the occurrence of SAS in T2DM patients.