Streptozotocin(STZ), a methylnitrosourea antibiotic, was investigated for its effect and possible mechanism (s) on the induction of gastric lesions, The study was performed in mice and Syrian Golden hamsters. Various doses of STZ ranging from 100 to 250 mg/kg BW were given to both species as a single intraperitoneal injection. The mice and hamsters were sacrificed at 6 weeks and 3 days after STZ injection, respectively. Incidence and severity of gastric lesions were progressively increased with the dose of STZ and correlated with the incidene and severity of diabetes mellitus mellitus (DM). The most effective dose was 200 mg.kg in both species. Gross and microscopic lesions in gastric mucosa occurred mostly as early as 1 week in the mice and 1 day in hamsters after the STZ injection and then progressively increased with time of observation. The severity of gastric lesions were assessed by both qualitative and quantitative methods which apparently detected at 3 weeks in the mice and 3 days in the hamsters. The gross gastric mucosal lesions in mice were hyperemia and bleeding sposts or sometimes streaks, whereas those in hamsters were pale-looking with or without erosions. Microscopic changes included vasocongestion, despuamation of the surface epithelium with deffuse hemorrhage and edema of mucosa as well as submucosa. Severe hyperglycemia was accompained by apparent impairments of liver and kidney including vacuolar degeneration and fatty changes of the organs. Liver and kidney function were assessed by SGOT and SGPT activities and BUN level. They revealed markedly damage of the organs. Quantitative assessment of gastric lesions was determined from Evans blue accumulation in the tissue. Evans blue content in gastric wall expressed as ...g/g stomach was markedly reduced to almonst a half of control. This finding may be resulted from either the reduced mucosal blood flow or vasoconstriction of vessels in the gastric mucosa. Two know protective agents against STZ-induces diabetes as well as insulin therapy were applied concurrently with STZ treatment to differentiate the direct action of STZ from the consequence effect of DM induced by STZ on the gastric mucosa. All agents used either nicotinamide (NA), 3-0-methly-glucose (3-OMG) or insulin at approgiate dose and time of treatment could ameliorate STZ-induced gastric lesions as well as the impairments of other organs, although DM was not completely prevented or reversed but it was markedly improved. In contrast, the animals which were resistant to the protective or curative agents remained being in severe diabetic state with severe gastric lesions as well as liver and kidney impairments. These results suggest that STZ might directly initiate lesions at the gastric mucosa. The aggravation of lesions to massive bleeding as well as erosions was apparent only in animals which presented with presistent metabolic alterration of DM.