In experiments on rats with modeled water-restrained stress, the influence of nonsteroidal anti-inflammatory drugs of different genesis on morphological status of gastric mucosa and changes of NO-synthase system parameters have been studied Administration of nonselective cyclooxygenese inhibitor naproxen in the water-restrained stress model in rats potentiated the increase of severity of damage of gastric mucosa. At the same time, the activity of both inducible and constitutive isoforms of NO-sythase decreased. The parameters of lipoperoxidation remained at the level observed during water-restrained stress. It was shown the advantages of the use of H2S-releasinfg nonsteroidal anti-inflammatory drug ATB-346, which are associated with its cytoprotective effect of the drug manifested by a decreased total area of gastric damage. However, parameters of lipoperoxidation and NOsyntase system did not differ substantially from those in the group treated with napoxen, indicating the prevalence of parent molecule (naproxen) in regulation of function of NO-system Administration of dual COX/LOX inhibitor, the compound 2A5DHT, caused a decrease of gastric damage as compared to the effect of naproxen. The activity of iNOS remained much higher than under condition of the naproxen action.