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Objective To investigate the the clinical application of triglyceride-glucose (TyG) index and its correlation with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods From January 2020 to December 2022，499 patients with T2DM were screened from the inpatients and physical examination populations of Nanjing Jiangbei Hospital. Based on the presence or absence of atherosclerotic plaques， the subjects were divided into T2DM with plaques group (n=249) and T2DM without plaques group (n=250). The subjects underwent medical history collection，physical examination，and serum biochemical testing. The TyG index was calculated，and the correlation between TyG and common risk factors for T2DM atherosclerosis was statistically analyzed. Results The age，systolic blood pressure (SBP)，triglyceride (TG)，total cholesterol (TC)，fasting blood glucose (FBG)，glycosylated hemoglobin (HbA1c)，and apolipoprotein A of the T2DM without plaques group were lower than those in the T2DM with plaques group, the diastolic blood pressure (DBP) was higher than that in the T2DM with plaques group (P＜0.05). The TyG index in the T2DM with plaques group was higher than that in the T2DM without plaques group (11.52±0.37 vs 9.34±0.48, t=56.803, P＜0.01). TyG index was positively correlated with age, SBP, TG, TC, low-density lipoprotein cholesterol (LDL-C), uric acid (UA), and HbA1c (P＜0.05)，and negatively correlated with high-density lipoprotein cholesterol (HDL-C) and fasting C-peptide (P＜0.05). The area under ROC curve of TyG index for predicting T2DM atherosclerosis was 0.611 ，with a best cut-off value of 10.21，sensitivity of 84.8%, and specificity of 62.2%. Conclusion TyG index is closely related to multiple risk factors for atherosclerosis in patients with T2DM. TyG index combined with risk factors for atherosclerosis can comprehensively assess the risk of T2DM atherosclerosis development.