Inspiratory flow limitation means that when the flowrate reaches a certain value, it no longer increases, or even decreases, which is called negative effort dependence flow limitation, even if the inspiration effort is increased. This occurs often in obstructive sleep apnea patients, but its mechanism remains unclear. To reveal the mechanism of inspiratory flow limitation, we constructed a unique partially collapsible in-vitro upper airway model of obstructive sleep apnea patients to observe the change of airway resistance with inspiratory driving pressure. The important findings demonstrate that with the increase of inspiratory effort, the driving pressure increases faster than the airway resistance in the early stages, and then the reverse occurs as the airway becomes narrower. The airway collapse caused by the transmural pressure can lead to a rapid increase in downstream resistance with the increase of inspiratory effort, which is the key reason causing the flow reduction and the formation of typical negative effort dependence flow limitation. The mechanical mechanism revealed in this study will lead to fully new insights into the study and treatment of obstructive sleep apnea.