Background: The noninvasive positive airway pressure ventilation (NPPV) has been widely applied in therapy for the respiratory patient in acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD), etc. Objective: In order to help clinician to investigate the technologies and measures of NPPV, a therapy system model included the respirator, breathing circuit and patient was designed. Methods: Consequently, the mathematical sub-models of respirator, breathing circuit and mask, and respiratory airway were developed. With these sub-models, the ventilation system model of NPPV was prepared. The MATLAB-Based simulation experimental platform of NPPV system was set up to conduct the simulation experiments. In addition, by using the active servo lung ASL5000, a physical experiment platform was designed for comparative tests. Both of simulated experiments and physical experiments were operated with the simulated patient in ARDS, COPD and patient without spontaneous breathing. Results: The simulated experimental outputs are coincident with the physical experimental outputs (P ≥ 0.31 with TTEST, R ≥ 0.92 with CORREL). Conclusions: The experimental results substantiated that the therapy system model of NPPV is operational and workable. With this system model, it will benefit clinicians and researchers to conveniently promote the development of NPPV.