Objective: To explore the relationship between the serum levels of Toll-like receptor 4 (TLR4) and glucose and lipid metabolism and chronic inflammation in patients with newly diagnosed type 2 diabetes mellitus. Methods: A total of 150 newly diagnosed type 2 diabetic patients and 45 normal controls in Department of Endocrinology of Second Hospital of Jilin University from September 2018 to January 2019 were enrolled. They were divided into three groups: a normal control group (NC group, n=45), a type 2 diabetes group (T2DM group, n=85), and a type 2 diabetes with overweight or obesity group (T2DM + OB group, n=65). Data including age, gender, disease duration, BMI, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), homeostasis modeall assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hs-CRP) were determined. The serum levels of TLR4 were determined by ELISA. The comparison between groups was tested by analysis of variance; correlation between serum TLR4 and BMI, TG, LDL-C, HOMA-IR and hs-CRP was performed by Pearson correlation analysis; logistic regression was used to analyze the independent risk factors of type 2 diabetes with overweight or obesity. Results: TG, LDL-C, FPG, HbA1c, FINS, HOMA-IR, hs-CRP and TLR4 in the NC group, the T2DM group and the T2DM+OB group gradually increased, and the difference among the 3 groups was statistically significant (P<0.05). There was a positive correlation between TLR4 with BMI, TG, LDL-C, HOMA-IR, and hs-CRP. Logistic stepwise analysis showed that LDL-C, HOMA-IR, hs-CRP and TLR4 were independent risk factors of type 2 diabetes with overweight or obesity. Conclusion: The higher the level of TLR4 in patients with newly diagnosed type 2 diabetes, the greater the risk of overweight or obesity.