In normal fed rats the low Km glucose transporter GLUT-1 is expressed only in one row of hepatocytes immediately surrounding a terminal hepatic venule, while the high Km GLUT-2 is expressed in every hepatocyte. Previously, we showed that additional perivenous hepatocytes express GLUT-1 in fasting animals. In diabetes, as in starvation, the liver functions to release glucose into the circulation, but unlike starvation, circulating extracellular glucose is high in diabetes. By immunofluorescence and Western blotting we studied whether glucose or insulin is the primary extracellular signal for inducing GLUT-1 expression in hepatocytes. We observed that streptozocin-induced diabetes causes induction of GLUT-1 expression in the plasma membrane of hepatocytes within four cell rows of a terminal hepatic venule; GLUT-2 expression is unaltered. Chronic insulin treatment of diabetic rats reduces the number of rows of hepatocytes expressing GLUT-1 from approximately four to approximately two. In contrast, chronic insulin infusion into nondiabetic rats does not affect the number of hepatocytes expressing GLUT-1. Thus, both fasting and diabetes induce GLUT-1 expression in specific hepatocytes that normally do not express this gene. This induction correlates with low insulin levels in the blood, and not with circulating glucose levels.