Diabetes mellitus is a metabolic disease characterized by hyperglycemia resulting from defective insulin secretion or resistance to insulin action, or both. Production of sugar alcoholes called as metabolic hypothesis, ischemia-hipoxia oxidative stress, and insufficiency of neurotrophin or non-neurotrophin growth factors play an important role in the pathogenesis of diabetic neuropathy. Cognitive deficiencies are also seen in diabetes. Hippocampus is an important brain region for cognitive functions and alterations in its function effects cognitive ability. Gliclazide is an oral antidiabetic agent, which attracts attention with its antioxidant properties and potentializing effects on insulin. The purpose of this study was to show the difference in effects of insulin and gliclazide theraphy on lipid peroxidation and antioxidant enzyme activities. For this purpose, we measured the lipid peroxidation as Thiobarbituric acid reactive substance and antioxidant enzyme (superoxide dismutase, catalase, glutathione peroxidase) activities by using spectrophtometric methods. in control (n=9), diabetic (n=9) and the diabetic groups, which were treated with insulin (n=7) and gliclazide (n=7). There was a significant increase in lipid peroxidation in the diabetic group (p<0,05). Either insulin or gliclazide treatment improved LPO in hippocampus similarly. Malondialdehyde levels were significantly different between the diabetic and insulin groups (p=0,021), and between the diabetic and gliclazide groups (p=0.020). The effects of insulin on the antioxidant enzyme activities were seen to be more evident. Consequently, there was no significant difference between the treatment with insulin and gliclazide in hippocampal LPO.