OBJECTIVE Clonidine, a known antihypertensive, is currently used for many purposes including diabetic gastroparesis, postmenopausal hot flushes, opioid/nicotine/alcohol withdrawal. Its effects on carbohydrate metabolism appear to be variable. Hence, the present study was undertaken to evaluate the influence of clonidine on euglycemic and alloxan -induced diabetic rats and its interaction with glibenclamide. METHODS Alloxan - induced (150 mg/kg, i.p) diabetic rats were divided into six groups of six animals each. Group I - Normal Control; Group II - Nondiabetic + Clonidine (25 mug/kg); Group III - Diabetic Control; Group IV - Diabetic + Glibenclamide (5 mg/kg); Group V - Diabetic + Glibenclamide + Clonidine. All drugs were given orally once daily. Blood glucose was estimated from rat tail vein using glucometer before start of the experiment and at the end of 30 days. RESULTS After 30 days of treatment, clonidine (25 mug/kg) produced significant hyperglycemia in both euglycemic and diabetic rats. It also reduced the hypoglycemic effect of glibenclamide in diabetic rats. CONCLUSIONS The results of present study indicate that clonidine has hyperglycemic effect and it also interacts with glibenclamide to reduce its hypoglycemic activity. If these findings are true to human beings then clonidine should not be used in diabetic patients on sulfonylureas.