Smoke inhalation injury is frequently accompanied by cyanide poisoning that may result in substantial morbidity and mortality, and methods are needed to quantitatively determine extent of airway injury. We utilized a 3-D endoscopic frequency-domain optical coherence tomography (FD-OCT) constructed with a swept-source laser to investigate morphological airway changes following smoke and cyanide exposure in rabbits. The thickness of the mucosal area between the epithelium and cartilage in the airway was measured and quantified. 3-D endoscopic FD-OCT was able to detect significant increases in the thickness of the tracheal walls of the rabbit beginning almost immediately after smoke inhalation injuries which were similar to those with combined smoke and cyanide poisoning.