The gastric mucosa plays an important role in the physiological function of the stomach. This mucosa acts as gastric barrier, which protects deeper located cells against the detrimental action of the gastric secretory components, such as acid and pepsin. Integrity of the gastric mucosa depends upon a variety of factors, such as maintenance of microcirculation, mucus-alkaline secretion and activity of the antioxidizing factors. The pathogenesis of gastric mucosal damage includes reactive oxygen species (ROS), because of their high chemical reactivity, due to the presence of uncoupled electron within their molecules. Therefore they cause tissue damage, mainly due to enhanced lipid peroxidation. Lipid peroxides are metabolized to malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). The local increase of MDA and 4-HNE concentration indicates ROS-dependent tissue damage. Superoxide dismutase (SOD) is the main enzyme, which neutralizes ROS into less noxious hydrogen peroxide. A decrease of SOD activity is an indicator of impairment of the protective mechanisms and significantly contributes to cell damage. Hydrogen peroxide is further metabolized to water in the presence of reduced glutathione (GSH). GSH can also work synergetically with SOD to neutralize ROS. The reactions between GSH and ROS yields glutathione free radical (GS(•)), which further reacts with GSH leading to free radical of glutathione disulphide (GSSG(•)). This free radical of GSSG can then donate an electron to the oxygen molecule, producing O2 (•-) Subsequently, O2 (•-) is eliminated by SOD. Adecrease of the GSH level has detrimental consequences for antioxidative defense cellular properties. Gastric mucosa, exposed to stress conditions, exhibits an enhancement of lipid peroxidation (increase of MDA and 4-HNE), as well as a decrease of SOD activity and GSH concentration. This chain reaction of ROS formation triggered by stress, appears to be an essential mechanism for understanding the pathogenesis of stress - induced functional disturbances in the gastric mucosa leading to ulcerogenesis.