SUMMARY. Due to its large surface area and its rich blood supply, the lung is susceptible to oxidative injury by many reactive oxygen species and free radicals. The main sources of oxidants affecting the lung include external agents (smoke, radiation, carcinogens, drugs, ozone, hyperoxia) and cellular mechanisms (inflammatory cells such as neutrophils, eosinophils, macrophages, fibroblasts, endothelial cells, xanthine and NADPH oxidases). Via these sources oxygen and nitrogen reactive species are produced, which exert the final harmful effect of cell damage. The major oxidative agents are the superoxide anion, hydrogen peroxide, the hydroxyl radical, nitric oxide, etc. Antioxidants help the lung to ward off the consequences of the oxidative injury. Antioxidant defenses include non-enzymatic agents (vitamins C and E, beta-carotene, uric acid) and enzymes (dismutase, catalases and peroxidases). New research has revealed the activity in antioxidant defense at a more subtle level of low molecular weight proteins such as oxygenase-heme, thioredoxins, etc. The susceptibility of the lung to oxidant injury depends mainly on the degree of its ability to upregulate the antioxidant defenses, which means that the various lung diseases attributed to oxidative injury could possibly be controlled by the antioxidant mechanisms at the cellular level or even at the level of gene expression. Antioxidant defense may be present at both cell and mRNA expression level, but antioxidant activity is the critical factor in the development and progression of lung disease. Pneumon 2007; 20(3):289-292