<h4>Background</h4>Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by elevated blood glucose.<h4>Objective</h4>This study is aimed at evaluating the efficacy of 4-methylesculetin in mitigating insulin resistance (IR) in HepG2 cells, thereby identifying the underlying mechanisms.<h4>Methods</h4>An HepG2 cell insulin resistance (IR-HepG2) model was established using high glucose and high insulin. This evidence concerns the gene INS and diabetes mellitus.