Intake of high sodium diet (HSD) has been implicated in development of insulin resistance and obese subjects are salt-sensitive. Recently, we reported that stimulation of angiotensin-II type 2 receptor (AT 2 R) by selective non-peptide agonist C21 prevents salt-sensitive hypertension and oxidative stress, however effect of AT 2 R activation on insulin resistance and circulating lipids in obese animals fed HSD is unknown. Therefore, we investigated effects of AT 2 R activation by C21 (1 mg/kg/day, s.c. by Alzet osmotic pump) on insulin resistance and circulating lipids in obese Zucker rats (OZR) fed HSD (4%) for 14 days. High-salt diet feeding significantly increased fasting plasma glucose (p<0.05) and insulin (p<0.05), and caused glucose intolerance as evident by oral glucose tolerance test (p<0.05). Concurrent treatment with C21 reduced plasma glucose (p<0.05) and insulin (p<0.05) and improved glucose tolerance (p<0.05). Circulating plasma free fatty acids (FFA) and triglycerides were unchanged in OZRs fed normal diet or HSD. Interestingly, however, C21 treatment lowered plasma FFA (p<0.05), but not triglycerides. Results suggest that AT 2 R activation may prevent onset of hyperglycemia in obese animals fed HSD by improving insulin sensitivity, however, target organ involved in AT 2 R-mediated effects remains to be explored.