Syrian Golden hamsters develop a more severe emphysema than Sprague Dawley rats after intratracheal instillation of the same dose of elastase/body weight. Although species variations in antielastase defenses may largely explain these results, other variables such as differences in lung antioxidants cannot be overlooked since oxidative sress is known to modulate antiprotease activity. We propose that elastase instillation might affect lung glutathione (GSH) metabolism differently in these species. Our aim was to study in hamsters and rats, lung glutathione metabolism at different times, from the stage of diffuse alveolar damage to advanced emphysema. We measured total and oxidized glutathione (GSSG) content as well as activity and expression of enzymes related to GSH synthesis and redox cycling: -glutamylcysteine synthetase (-GCS), glutathione peroxidase (GPx) and glutathione reductase (GRd). Whereas rats showed no significant changes in these measurements, hamsters showed significant derangement in GSH metabolism early after elastase instillation: a 25% fall in total GSH (p<0.05) with no increase in GSSG associated with reduction in enzyme activity 24 hours after elastase (60% for -GCS (p<0.01), 30% for GPx (p<0.01) and 75% for GRd (p<0.001). GSH homeostasis was restored at the end of the first week, involving a transient increased expression of the three enzymes. We conclude that elastase induces significant alterations in GSH metabolism of hamster lungs and no overall change in rat lungs. We propose that hamsters become vulnerable to functional inhibition of 1-AT by oxidants and thus, more susceptible to injury than it would be considering only their low 1-AT level.