There is evidence that oxidative stress might be implicated in promoting a state of systemic inflammation in diabetic patients. Understanding the role of reactive oxygen species in the inflammatory response in diabetes becomes essential in finding preventive treatments. Pioglitazone is a new oral antidiabetic agent with potent antioxidant and anti-inflammatory properties. The drug is a high affinity ligand of peroxisome proliferator-activated receptor gamma. This receptor seems to be involved in the control of inflammation by modulating the production of inflammatory mediators. In the present study, the changes in some markers of enhanced oxidative stress and in the level of pro-inflammatory interleukin-6 (IL-6) were examined in plasma of diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. Ascorbic acid (AA) concentration and total antioxidant status (TAS) in plasma of diabetic animals were diminished and significantly elevated after pioglitazone treatment (p < 0.05). Protein carbonyl groups (PCG) content and IL-6 concentration were elevated in plasma of diabetic animals and significantly diminished after pioglitazone treatment. The results obtained in the present study confirm the relations of cytokine systems with oxidative stress in plasma of diabetic subjects. They also suggest the antioxidative and antinflammatory properties of pioglitazone.