Background: Sitagliptin is a dipeptidyl peptidase type 4 inhibitor. This study was done to assess the insulin-sensitizing effect of sitagliptin on Wistar albino rats by means of surrogate measures. Methods: There were four groups of six rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received sitagliptin 100 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Fourth group did not receive any medication and was considered as normal control. Fasting blood sugar, lipid profi le, blood sugar 2 hrs after glucose load (postprandial blood sugar), liver weight, liver volume, and histopathological analysis were done. Results: The effects of sitagliptin were compared with that of pioglitazone. Dexamethasone caused hepatomegaly, dyslipidemia, and hyperglycemia. Both pioglitazone and sitagliptin signifi cantly reduced hepatomegaly, dyslipidemia, and hyperglycemia (p<0.01). Reduction of blood sugar levels after glucose load was signifi cant with pioglitazone in comparison to sitagliptin (p<0.01). Conclusions: Sitagliptin has comparable effi cacy to pioglitazone in dexamethasoneinduced hepatomegaly, dyslipidemia, and fasting hyperglycemia.