Water nitrate pollution has been demonstrated to induce pancreatic toxicity, with an increased risk of developing diabetes and exocrine pancreatic cancer. This study aimed to evaluate mechanisms that lead to pancreatic toxicity in nitrate exposed young and adult male rats, as well as the preventive effect of fenugreek seeds against these changes. Nitrate exposure of both ages showed almost identical changes, including a significant reduction in serum insulin with elevation in blood glycosylated hemoglobin, serum glucose, acid phosphatase, α-amylase, and pancreatic tumor marker (carcinoembryonic antigen), indicating a tendency for developing diabetes, in association with pancreatic cancer which seemed of greatest value in the young group. An elevation in pancreas levels of nitric oxide, hydrogen peroxide, and lipid peroxidation, with a reduction in the antioxidants; superoxide dismutase and catalase, as well as glutathione and its metabolizing enzymes; glucose -6- phosphate dehydrogenase and γ- glutamyl transferase were also demonstrated. This goes with marked changes in insulin gene profile, as indicated by the appearance of a new band with a molecular weight of 275 bp and absence of three (1100, 825, and 750) bands as compared to the control of each age. Feeding fenugreek seeds powder to all nitrate exposed rats prevented changes in serum glucose, insulin, pancreatic tumor marker, oxidative stress biomarkers, and insulin gene profile, indicating the effectiveness of this plant to elicit cytoprotection against nitrate – induced pancreatic toxicity, probably through its antioxidant properties.