Background and Objective <p>Type 2 diabetes mellitus (T2DM) is a group of metabolic diseases characterized by chronic hyperglycemia, primarily caused by insulin resistance and/or pancreatic beta cell dysfunction. Glibenclamide, a second-generation sulfonylurea oral hypoglycemic agent, plays a crucial role in managing T2DM.&#xa0;Our objective was to establish a population pharmacokinetic&#xa0;model of glibenclamide in Chinese healthy volunteers and use this model to guide the adjustment of individualized dosage regimens.</p> Methods <p>We collected 476 concentration observations of glibenclamide from 20 Chinese healthy volunteers in a phase I clinical trial. A fundamental three-compartment pharmacokinetic model with instantaneous zero-order absorption and linear elimination was developed using the first-order conditional estimation method by NONMEM software. A covariate model was developed by screening for relevant covariates based on the base model. Internal validation of the final model was performed using visual predictive checks and bootstrap methods. The reference standard for the final model was used to assess the quality of the simulated doses.</p> Results <p>A PopPK model of glibenclamide in Chinese healthy volunteers was successfully established. Age significantly impacted the apparent distribution volume of the central compartment. Validation results indicate that the final model is stable. Simulation results indicate that the model has good goodness of fit.</p> Conclusions <p>The established population model accurately represents the pharmacokinetics of glibenclamide in Chinese healthy volunteers and based on this model, can be further extrapolated to inform individualized medication strategies for glibenclamide in the treatment of T2DM in the future.</p>