OBJECTIVE: Obesity and insulin resistance carry a high risk of progressing to type 2 diabetes mellitus. A lot of evidence has tightly associated insulin resistance with chronic inflammation. Besides, it has been reported the activation of amphiregulin epidermal growth factor receptor pathways is involved in chronic inflammation. The aim was to evaluate the relationship between insulin resistance and amphiregulin. METHODS: Data from 203 volunteers was collected from November 2020 to June 2023 visiting the Affiliated Suzhou Hospital of Nanjing Medical University, Jiangsu, China. The serum levels of amphiregulin and diabetes related parameters were measured in all participants. The correlation analysis and multiple stepwise regression of amphiregulin and some diabetes indicators were performed in all groups. RESULTS: The concentrations of amphiregulin were 143.29pg/ml, 163.29pg/ml, 158.92pg/ml, 171.89pg/ml, 155.03pg/ml in the normal, obesity, non-obese diabetes, obese diabetes and obese diabetes after therapy groups (p <
0.01), and the homeostasis model assessment index were 1.6, 4.01, 3.93, 6.67 and 3.4 respectively (p <
0.01). Moreover, amphiregulin positively correlated with the homeostasis model assessment index in each separated group and the total sample (r=0.644, p <
0.01). Meanwhile, the regression analysis showed a strong, positive association between amphiregulin and the homeostasis model assessment index (p <
0.01). More importantly, this correlation remained after obese diabetes patients treated with drugs to relieve insulin resistance. CONCLUSION: Amphiregulin is up-regulated in obese individuals than normal size people whether diabetics or not, and positively correlates with the homeostasis model assessment index, which suggesting early signs of insulin resistance and abnormal glucose metabolism.