Objective: Wild musk melon (Cucumis melo var.agrestis,CMA) is one of the edible plants form Tamil Nadu.Traditionally,this plant was used as diabetic diet (leaves of CMA with Momordica charantia leaves),but there is no scientific report on antidiabetic action of this plant material.Hence,the current research work was designed to evaluate the antihyperglycemic and antihyperlipidemic effect of hydroalcoholic extract of CMA leaves (HALEC) in streptozotocin (STZ)-nicotinamide (NIC)-induced diabetic rats.Methods: Diabetes was induced by administration of STZ (60 mg/kg,i.p.) after 15 min of NIC (120 mg/kg i.p.) administration.The diabetic rats were treated with HALEC (300 and 600 mg/kg,p.o.,respectively)for 21 d.Results: After the management with HALEC,blood glucose,HbA1c levels,total cholesterol,LDL cholesterol,triglycerides levels,glycogen phosphorylase and glucose-6-phosphatase levels were significantly diminished in diabetic rats.However,haemoglobin level,HDL cholesterol,liver glycogen,total protein,hexokinase,glucose-6-phosphate dehydrogenase levels were significantly increased in HALEC treated diabetic rats.The histopathological studies of the pancreas in HALEC-treated diabetic rats showed almost normal appearance.L6 cell line study revealed the increased glucose uptake activity of HALEC.High performance thin layer chromatography (HPTLC) analysis confirms the presence of active principles such as rutin,gallic acid and quercetin in HALEC.Conclusion: The results indicated that HALEC possess significant antihyperglycemic and antihyperlipidemic activity in STZ-NIC-induced type Ⅱ diabetic rats with protective effect.This research work will be useful for the isolation of active principles and development of herbal formulation in phytopharmaceuticals.