Fire accident victims, who sustain both thermal injury to skin and smoke inhalation, have gross evidence of systemic and pulmonary oxidant damage and acute lung injury. We hypothesized that gamma-Tocopherol (gT), a reactive O 2 and N 2 scavenger, when delivered into the airway will attenuate lung injury induced by burn and smoke inhalation. Acute lung injury was induced in chronically prepared, anesthetized sheep by 40% total burn surface area, 3rd degree skin burn and smoke insufflation (48 breaths of cotton smoke, <40°C). Study groups: 1) Sham (not injured, flax (FO)-nebulized, n=6); 2) SA-neb (injured, saline-nebulized, n=6); 3) FO-neb (injured, FO-nebulized, n=6); 4) gT+FO-neb (injured, FO+gT-nebulized, n=6). Nebulization was started 1 h post-injury and 24 ml of FO with or without gT (51 mg/ml) was delivered into airways over 47 h using our newly developed lipid aerosolization device (droplet size-2.5-5 μm). The burn and smoke inhalationinduced pathological changes seen in the saline group were attenuated by FO nebulization; gT addition further improved pulmonary function. Pulmonary gT delivery along with a FO source may be a novel effective treatment strategy in management of patients with acute lung injury.