Introduction: Diabetes mellitus (DM) is a global emerging disease with progressive incidence worldwide. Diabetic patients have a higher incidence of peptic ulcer disease than the non-diabetic population. So, diabetic patients treated with oral antidiabetic drugs, as gliclazide, may be also treated with antipeptic ulcer drugs, as omeprazole. Aim of the Study:Evaluation of the possible drug-drug interactions between gliclazide and omeprazole in alloxan-induced diabetic rats. Materials and Methods:The study was done on 40 adult male albino rats (250-300 gm) classified into five groups. Diabetes was induced in group II, III, IV &V using alloxan monohydrate while group I was left as a negative control. Group II received no treatment, group III received gliclazide, group IV received omeprazole, while group V received combination of gliclazide and omeprazole. After the end of the experiment, rats were sacrificed and blood samples were collected for measurement of glucose, insulin, total antioxidant capacity (TAC), tumor necrosis factor-α (TNFα) level. Also, histopathological study of the pancreas specimens was done. Results:diabetic rats showed significant increase in serum glucose level compared to normal rats. Treatment with gliclazide, omeprazole or combination of them had significant decrease in high serum glucose level. Serum insulin level in diabetic rats had significant decrease compared to normal rats. While, Treatment with gliclazide, omeprazole or combination of them had significant increase in its low level. Besides, diabetes in rats caused significant decrease in TAC compared to normal rats. Treatment with gliclazide, omeprazole or combination of them had significant increase in its low level. Regarding TNF-α, alloxan-induced diabetes in rats caused significant elevation in its level compared to normal rats. Treatment with gliclazide, omeprazole and combination of gliclazide and omeprazole caused significant reduction in its high level. Conclusion: The antidiabetic action of gliclazide was enhanced by omeprazole.