Objective:To build PBPK/PD models subcutaneous exposured to chlorpyrifos. Methods:①Animalt:Adult female SD rats were randomly divided into 3 treated groups and 1 control group. Subcutaneous injection was performed for once,and biological samples were collected at 3,6,12,24,48,72 hours. The indicators included serum CPF,TCP and urine,serum acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). ②The establishment of models:a:Determination the model structure. b:Set up of differential equation,and collection the parameters of model. c:Simulation. Optimize the model parameters. d:Validation of models. Results:The PBPK/PD model parameters was optimized according to experimental data of 139.5 mg/kg group. Changes of CPF,TCP and ChE were mocked in this model,and the simulation results were good. The experiments and model simulation results showed that CPF and TCP in serum increased initially and then decreased. ChE activity in serum decreased initially and then increased. Experimental data showed that serum CPF and TCP reached peak at 6-hour and 12-24-hour after exposure,respectively. Serum AChE and BuChE activity achived the minimum at 24-hour and 12-24-hour,respectively. Model simulation data showed that serum CPF and TCP reached peak at 6.7-hour and 24.7-hour,respectively. Serum AChE and BuChE activity achived the minimum at 32-35-hour and 15-28-hour,respectively. Conclusion:PBPK/PD models can simulate the disposal process of CPF,TCP and ChE.