Smoke inhalation injuries are the leading cause of mortality from burn injury. Airway obstruction due to mucus plugging and bronchoconstriction can cause severe ventilation inhomogeneity and worsen hypoxia. Studies describing changes of visco-elastic characteristics of the lung after smoke inhalation are missing. We present results of a new smoke inhalation device in sheep and describe patho-physiological changes after smoke exposure. Methods. Fifteen female Merino ewes were anaesthetized and intubated. Baseline data using electrical impedance tomography (EIT) and multiple breath inert gas washout (MBW) were obtained measuring ventilation distribution, functional residual capacity (FRC), lung clearance index (LCI), dynamic compliance (Cdyn) and stress index (SI). Ten sheep were exposed to standardized cotton smoke insufflations and five sheep to sham smoke insufflations. Results. Measured COHb before inhalation was 3.87 ± 0.28 % and 5 minutes after smoke 61.5 ± 2.1%, range 50-69.4% (P < 0.001).Two hours after smoke FRC decreased from 1773 ± 226 mL to 1006 ± 129 mL and LCI increased from 10.4 ± 0.4 to 14.2 ± 0.9. Cdyn decreased from 56.6 ± 5.5 mL/cmH2O to 32.8 ± 3.2 mL/cmH2O. SI increased from 0.994 ± 0.009 to 1.081 ± 0.011 (P < 0.01); (all mean ± SE, P < 0.05). EIT showed a shift of ventilation from the dependent to the independent lung after smoke. No significant change was seen in the sham group. Conclusion: Smoke inhalation caused immediate onset in pulmonary dysfunction and significant ventilation inhomogeneity. The new smoke inhalation device as may be useful for interventional studies.