Pulmonary system is a target organ and primary defense mechanism against environmental oxidants and polutants. Enzymatic and nonenzymatic antioxdant defense mechanisms undoubtedly protect the lung from oxidants even endogenous oxidative stress. In addition, new ways of augmenting pulmonary antioxidant defenses are developed, which can be used to support the intrinsic antioxidants. Therefore, improved understanding of antioxidant defense mechanisms will increase our knowledge of the cause and will suggest rational approaches for treating and preventing oxidant-induced lung injury. In this review, we discuss the formation and scavenging of free radicals, and the strategies for antioxidant defense of pulmonary system.