Oxidative stress and post-ischemic inflammatory response are the key pathogenic mechanisms of the neuronal injury caused by ischemic stroke (IS). On the other hand, Diabetes is a major risk factor for the development of stroke, increasing the susceptibility to atherosclerosis and the prevalence of atherogenic risk factors, including hypertension, obesity, and abnormal blood lipids. The aim of current study was to analyze the functional activity of oxidant-antioxidant system and post-ischemic inflammatory response in IS patients complicated and noncomplicated with diabetes mellitus type 2 (DM2). ELISA, photochemiluminescent and spectrophotometric methods were used to analyze the serum samples of IS patients complicated and noncomplicated with DM2, DM2 patients, as well as healthy subjects. The results obtained suggest that IS complicated with diabetes is characterized by higher intensity of the lipid peroxidation process as compared to IS noncomplicated with diabetes that, probably, is one of the determining factors responsible for more severe clinical course of IS patients complicated with DM2 compared to those noncomplicated with DM2. It is also shown that mechanisms of the compensatory response to oxidative stress on the level of antioxidants in IS patients complicated with diabetes differ from those detected in IS noncomplicated with diabetes. A significant increase of the levels of the five analyzed cytokines in both groups of IS patients were detected. Based on the results obtained we suggest that metabolic, molecular, and cellular level alterations are typical for long-term DM2 impair compensatory mechanisms protecting the body from oxidative stress, and that in IS complicated with DM2 the systemic inflammatory reactions and oxidative stress are more intense than in case of IS noncomplicated with DM2.