Aim: Oxidative stress during early phase of acute hypobaric hypoxia may predispose an individual susceptible to critical altitude illness while ascending rapidly to high altitudes. We assessed the biochemical parameters and examined the histological changes to check the oxidative stress status of the lung tissues of Sprague-Dawley rats, susceptible and tolerant to acute hypobaric hypoxia during early phase of exposure. Methods: A simulated acute hypobaric hypoxia of one hour at 9144 m and 24°C was given to susceptible male, normal male (moderate), tolerant male and female groups of rats. Reactive oxygen species (ROS) levels, malondialdehdye (MDA) and oxidized glutathione (GSSG) content, total catalase (CAT) activity, superoxide dismutase (SOD) inhibitory activity and glutathione peroxidase (Gpx) activity were measured using standard protocols in lung tissue samples isolated from the different groups of hypoxia stressed and normoxic rats. Histological changes were also studied by haematoxylin and eosin staining in these tissue samples. Results: Marked neutrophil infiltration, alveolar wall collapse and interstitium thickening was visible in susceptible lung tissues showing maximum ROS levels, MDA equivalents and GSSG activity comparative to other test samples. Although SOD inhibitory activity increased in susceptible and normal groups in comparison to both the tolerant groups, however, Gpx activity showed an opposite trend. Catalase activity was recorded highest in the normal rat group as compared to other groups. Conclusion: Increased neutrophil infiltration coupled with higher oxidant’s levels in susceptible rat lungs, and increased antioxidant enzyme activity in normal and tolerant rats demonstrate the differential physiological states in lung tissues, which could be diagnosed even in early phase of acute hypobaric hypoxia stress.