Knowledge of the mechanical behavior of immature airways is crucial to understand the effects exerted by ventilation treatments, namely by total liquid ventilation (TLV). A computational approach was adopted to investigate the behavior of preterm lamb airways in the range of pressure applied during TLV. A 3D finite-element parametric structural model of the trachea, carina and first bronchi was developed using Gambit 2.1. Structural analyses were performed using ABAQUS/Standard 6.4 to evaluate airway deformation during TLV. The model consists of 7 rings composed of 3 tissues (cartilage, smooth muscle, connective tissue) modelled as hyperelastic materials. Biomechanical tensile tests were performed on preterm lambs' tracheae to obtain the stress-strain relationship for each tissue. After pretensioning the model (10% in longitudinal direction), positive and negative pressures (range +25 to -60 cmH2O) were applied on the internal surface of the modelled rings (step 5 cmH2O). The resulting displacement fields of the internal lumen for 4 deformed configurations were used to perform steady state fluid-dynamics numerical simulations (Fluent 6.2) in order to determine the shear stress distribution on the inner wall induced by the perfluorocarbon expiratory flow (7.7 ml/s). κ-ω viscous model was chosen, being suitable for low-Reynolds flows and accurate shear stress quantification. The near-wall mesh was refined to obtain y+ value of the boundary layer cells ranging within 1 to 5, so that the Enhanced Wall Treatment Method could be used for the shear stress evaluation. The structural analysis shows progressive lumen narrowing during expiration, at increasing negative pressure until the occurrence of collapse, however, not resulting in complete occlusion. Maximum (+1.2 MPa) and minimum (-1.6 MPa) principal stresses on airway wall were located on the cartilaginous rings at -60 cmH2O. Model reliability was verified by comparing the outcomes of the simulations to CT scan images acquired during in vivo TLV trials. Shear stress on the inner airway wall was determined on the 4 configurations: as the intraluminal pressure decreases, the shear stress value increases (3.6 Pa at 0 cmH2O, 20.4 Pa at -15cmH2O, 65 Pa at -30 cmH2O, 120 Pa at -60 cmH2O). A reliable structural model, capable of properly reproducing and predicting the behavior of tracheae and main bronchi during the respiratory cycle, was obtained; this model proved to be reliable and flexible, thus helping to set the ventilation parameters (e.g., tidal volume, expiratory pressure) during TLV. The progressive reduction of the cross section, during airway collapse, induces an increase in the velocity gradients and consequently the rising of shear stress values on the internal walls; further studies will be performed, in order to identify incidental tissue damage, induced by shear stress.