Objective T o analyze the influence of high flow nasal cannula (HFNC) on trespiratory mechanical parameters of the patient with acute respiratory distress syndrome (ARDS) based on ventilation experiment, and investigate the therapeutic and side effects of the HFNC. Methods The HFNC ventilation system model based on MATLAB and the physical experiment platform based on active simulated lung ASL5000 were developed to simulate the respiratory movement of ARDS patients with different lung compliance, and a series of the HFNC ventilation experiments were carried out. Both experimental results in MATLAB and physical platform were compared and analyzed. Results The results from the Matlab model-based simulation experiment and physical platform based-physical experiment uniformly showed that increasing the output flow of HFNC would decrease the relevant respiratory mechanical parameters of respiratory flow and tidal volume, but increase the intrapulmonary pressure and the functional residual capacity (FRC). Under the condition of small flow, the output flow from HFNC might be smaller than the inspiratory flow required by the patient, and an inspiratory compensation flow was necessary to make up for the inspiratory flow. Conclusions The necessary reliable compensation flow in inspiration will promote the security of HFNC. Understanding the changes in respiratory mechanical parameters of ARDS patient will be beneficial to pre-evaluate the HFNC, improve the ventilation effect and reduce the ventilation risks.