Objective To establish a model of respiratory mechanics with consideration of gas exchange and directly correlate with the gas content in blood during mechanical ventilation with the mechanics of respiratory system. Methods By coupling the physiological parameters of respiratory system and blood circulation system, including the molecular numbers of oxygen and carbon dioxide in alveoli and clinically monitored physiological parameters such as gas content, hemoglobin content, heart rate and cardiac output, a mechanical model was constructed to predict those dynamic parameters of gas content, pressure and flow rate in airway and alveoli in continuous breathing cycles. Results The gas content in different locations of a respiratory system was estimated by the model and the sensitivity of gas content in expiration to the undetermined parameters was evaluated. Conclusions The model of respiratory mechanics developed in the study is a preliminary attempt to predict the regulation roles of physiological parameters clinically monitored during mechanical ventilation, which will provide a theoretical support for the design and development of novel respirators in the follow-up experiment.