Objective To use PBPK model to predict the tissue distribution of quercetin in human , and analyze its distribution and metabolic transformation process in different physiological compartments, so as to supplement the deficiency of human experimental data, and provide important technical support for health risk-benefit assessment and safe intake formulation of quercetin. Methods Based on the physicochemical properties of quercetin, physiological parameters of rats and ADME parameters, a rat physiological pharmacokinetic (PBPK) model was constructed by GastroPlus software. The predicted concentration-time curve of the model was compared with the measured data to verify the accuracy of the main pharmacokinetic parameters. The model is further extrapolated to human PBPK model, and the accuracy, sensitivity and correlation analysis are completed. Results The predicted and measured ratios of major pharmacokinetic parameters of PBPK models in rats and human were within the error range of 0.5 to 2 times, and the average folding error and absolute average folding error were both at acceptable levels, indicating that the model was well fitted and the prediction results were highly reliable. Conclusion The physiological pharmacokinetic model of rats was successfully constructed, and based on this model, the human pharmacokinetic behavior was predicted, which provided a new idea for efficient and safe use and management of quercetin.