The euglycemic-hyperinsulinemic clamp technique in conscious Sprague-Dawley and Wistar rats chronically instrumented with intravascular catheters and pulsed Doppler flow probes was used to examine insulin's actions on regional blood flow and glucose metabolism. The effect of insulin on in vivo and in vitro glucose utilization in individual muscles was estimated using [3H]-2-deoxy-D-glucose. We found that in both strains, insulin (4, 32, and 64 mU x kg(-1) x min(-1)) causes similar cardiovascular changes characterized by slight increases in blood pressure (at high dose), vasodilation in renal and hindquarter vascular beds, and vasoconstriction (at high dose) in the superior mesenteric vascular bed. However, at the lowest dose of insulin tested, we found a smaller insulin sensitivity index and a lower insulin-stimulated in vivo glucose uptake in extensor digitorum longus (EDL) muscles of Wistar versus Sprague-Dawley rats. Higher insulin-stimulated glucose transport activity was found in isolated soleus muscle, while greater basal glucose transport was noted in isolated EDL muscle from Sprague-Dawley versus Wistar rats. These results provide further evidence for an insulin blood flow-regulatory effect and suggest that strain characteristics (differences in muscle perfusion, hindquarter composition, or fiber insulin sensitivity) constitute a major determinant in the variation in whole-body insulin sensitivity.