The role of insulin sensitivity (IS), as well as the association of IS with fibrinolysis impairment, in the occurrence of ischemic stroke, has not been clarified. The study was aimed to analyze IS, plasma insulin (PI) and plasminogen activator inhibitor (PAI)-1 levels in 34 type 2 diabetics (T2D) with ischemic stroke (group A), 30 T2D without ischemic stroke (group B), 33 nondiabetics with ischemic stroke (group C) and 33 healthy controls (group D). Ischemic stroke was confirmed by clinical and neuroimaging criteria. IS levels were determined by the minimal model analysis (Si index). Plasma insulin levels were measured by radioimmunoassay and PAI-1 activity was performed by the plasminogen chromogenic plasmin substrate assay. We found that Silevels were significantly lower in group A vs. B (1.17+/-0.66 vs. 2.79+/-0.62 min-1/mU/Lx104; p<0.001) and in C vs. D (3.25+/-0.84 vs. 6.03+/-1.69 min-1/mU/Lx104; p<0.001), while PI levels were higher in group A vs. B (19.46+/-4.11 vs. 14.79+/-1.75 mU/L; p<0.001) and in C vs. D (15.16+/-2.23 vs. 7.54+/-2.03 mU/L; p <0.001). Also, PAI-1 activity was significantly higher in group A vs. B (7.78+/-1.05 i 4.56+/-0.71 mU/L; p<0.001) and in C vs D (4.65+/-0.69 i 3.48+/-1.29 mU/L; p<0.001). Moreover, Silevels correlated with PAI-1, both in T2D and nondiabetics. Our results indicate that appearance of ischemic stroke was associated with decreased insulin sensitivity, together with compensatory hyperinsulinemia, both in T2D and nondiabetics. Our results imply that impaired insulin sensitivity exerts its atherogenic influence, at least in part, by decreased fibrinolysis.