We analyzed (a) insulin sensitivity (IS) and (b) glutathione peroxidase (GSH-Px), glutathione reductase (GR), and superoxide dismutase (SOD) antioxidant enzyme activity in type 2 diabetic (T2D) patients with atherothrombotic infarction (ATI) (group A), lacunar infarction (LI) (B), or without stroke (C) and in nondiabetics with ATI (D), LI (E), or without stroke (F). ATI and LI were confirmed by brain imaging IS levels were determined by minimal model (Si index), and the enzyme activity by spectrophotometry. In T2D patients, Si was lower in A and B versus C (1.14±0.58,1.00±0.26versus3.14±0.62 min⁻¹/mU/l × 10⁴,P<0.001) and in nondiabetics in D and E versus F (3.38±0.77,3.03±0.72versus6.03±1.69 min⁻¹/mU/l × 10⁴,P<0.001). Also, GSH-Px and GR activities were lower in A and B versus C (GSH-Px:21.96±3.56, 22.51±1.23versus25.12±1.67; GR:44.37±3.58, 43.50±2.39versus48.58±3.67 U/gHb;P<0.001) and in D and E versus F (GSH-Px:24.75±3.02, 25.57±1.92versus28.56±3.91; GR:48.27±6.81, 49.17±6.24versus53.67±3.96 U/gHb;P<0.001). Decreases in Si and GR were significantly related to both ATI and LI in T2D. Our results showed that decreased IS and impaired antioxidant enzymes activity influence ischemic stroke subtypes in T2D. The influence of insulin resistance might be exerted on the level of glutathione-dependent antioxidant enzymes.