We investigated the effect of peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists on serum vascular endothelial growth factor (VEGF) in diet-induced insulin resistant SD rats and ZDF rats. SID rats fed a high fat/sucrose diet showed increases in serum insulin and VEGF (both p < 0.01). Treatment with a PPAR gamma agonist G1262570 normalized the diet-elevated insulin and VEGF (both p < 0.0 1). There was a positive correlation between serum insulin and VEGF (p < 0.05) in SID rats. ZDF rats had higher serum glucose, insulin, and VEGF than Zucker lean rats (all p < 0.01). Treatment of ZDF rats with PPAR7 agonist pioglitazone decreased serum glucose and VEGF (both p < 0.01). There was a positive correlation between glucose and VEGF in ZDF rats (1) < 0.05). In 3T3-LI adipocytes, G1262570 did not affect insulin-stimulated VEGF secretion. These studies demonstrated that hyperinsulinemia in SID rats and hyperglycemia in ZDF rats were associated with increased serum VEGF; PPAR gamma agonists normalized serum insulin, glucose, and VEGF, but did not affect VEGF secretion in vitro. (c) 2005 Elsevier Inc. All rights reserved.