Background: Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (V T ) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs. Methods: One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three V T (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH 2 O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regionsof-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and V T ) was used, with a three-way mixed analysis of variance (ANOVA). Results: Two-way interactions between PEEP and group, and V T and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and V T in the injured group than in the control group. A two-way interaction between PEEP and V T was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups. Conclusions: Large PEEP and V T levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.