Background and aims: Overproduction of nitric oxide via inducible nitric oxide synthase (iNOS) is suggested to be a significant pathogenic factor in Helicobacter pylori induced gastritis. The purpose of this study was to examine the role of iNOS in H pylori associated gastric carcinogenesis. Methods: Two types of mice were used in this study: iNOS deficient mice (iNOS2/2) and wild-type littermates. Gastric cancer was generated in mice using a combination treatment comprising N-methyl-Nnitrosourea administration and H pylori infection. Fifty weeks after treatment, tumours in gastric tissues from both types of mice were examined using histopathology, immunohistochemistry, and immunoblotting for iNOS and 3-nitrotyrosine. Results: The overall incidence of gastric cancer at week 50 was significantly lower in iNOS2/2 compared with iNOS wild-type mice (p,0.05). When analysed according to tumour pathology, the incidence of gastric adenocarcinoma was significantly lower in iNOS2/2 compared with iNOS wild-type mice (p,0.05). Immunostaining for iNOS was clearly observed in adenocarcinoma cells of iNOS wild-type mice, and was characterised by a strong cytoplasmic expression pattern. 3-Nitrotyrosine was expressed mostly in the area of the lamina propria of gastritis and adenoma lesions in iNOS wild-type mice. Immunoblotting analyses showed that iNOS and 3-nitrotyrosine were also expressed in both adenoma and adenocarcinoma tissues from iNOS wild-type mice. iNOS and 3-nitrotyrosine expression was greater in tumour tissues than in non-tumour tissues. Conclusions: These findings suggest that iNOS contributes to H pylori associated gastric carcinogenesis in mice.