During the past few years many phytochemicals responsible for anti-diabetic effects have been isolated from the plants. Several phytoconstituents such as alkaloids, glycosides, flavonoids, saponins, dietary fibers, polysaccharides, glycolipids, peptidoglycans, amino acids and others obtained from various plant sources that have been reported as potent hypoglycemic agents. In the present study, the effect of methanolic extract of whole plant of Lindernia ciliata (LCME) (100, 200 and 400 mg/kg) on glucose levels in streptozotocin (STZ) (45 mg/kg) induced diabetic rats was investigated using glibenclamide 10 mg/kg as the positive control. The effect of the extract on body weight, insulin, total cholesterol, triglycerides, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total protein, serum urea, creatinine and hematological indices in normal, treated and untreated diabetic rats was investigated. Induction of diabetes in male Wistar rats (200-250 g) resulted in increased levels of serum glucose, total cholesterol, triglycerides, SGOT, SGPT, ALP, urea and creatinine and decreased bodyweight, serum insulin, total protein, RBC, WBC and hemoglobin levels. Administration of the extract at three test doses resulted in significant reduction in the levels of serum glucose, total cholesterol, triglycerides, SGOT, SGPT, ALP, urea and creatinine and significant increase in the body weight, insulin, total protein, RBC, WBC and haemoglobin levels which were observed in STZ-induced diabetic rats after 21 days of the treatment with the extract. At 200 mg/kg, LCME showed significant (p˂0.01) reduction in plasma glucose levels compared to glibenclamide (10 mg/kg). The results indicate that methanolic extract of whole plant of Lindernia ciliata possesses significant antidiabetic activity. INTRODUCTION: Diabetes is a metabolic disorder characterized by chronic hyperglycemia and alterations in carbohydrate, protein and lipid metabolism with absolute or relative deficiencies in insulin secretion and/or insulin production 1 .