Objective To realize the online estimation of airway resistance ( R) by applying positive airway pressure in ventilation treatment. Methods At the end of expiration when the airflow was zero, with a negative pulse pressure superposed upon the expiratory positive airway pressure (EPAP), a discharged airflow in the airway was produced, and the R and C were calculated with the discharged airflow. Then, taking the simulated normal adult, typical patients with acute respiratory distress syndrome (ARDS) and patient with chronic obstructive pulmonary disease (COPD) as experimental subjects, a simulated platform was established and the simulation experiments were conducted to calculate R and C. Results The errors in R and C were 3. 398% and -3. 288% for the simulated normal adult, 1. 265% and -1. 348% for the simulated patient with COPD, 3. 400% and -3. 286% for the simulated patient with ARDS, respectively. Conclusions The method with a negative pulse pressure superposed upon the EPAP to conduct the R and C is well practicable. This study lays solid foundation for the technology of intelligent and precision ventilation.