Ethnopharmacological relevance: "Urtica pilulifera has been traditionally used in Egyptian system as an herbal remedy to be a diuretic, antiasthmatic, anti-inflammatory, hypoglycemic, hemostatic, antidandruff and astringent" Aim of the study: To evaluate the potential effects of ethyl acetate (EA), chloroform (CHLOR) and hexane (HEXA) extracts of Urtica piluliferaas oral anti-diabetic agents as well as to evaluate their possible antioxidant and anti-inflammatory effects in type2 diabetic rat model. Material and methods: Type2 diabetes was induced by a high fat diet and low dose streptozotocin (STZ). Diabetic adult male albino rats were allocated into groups and treated according to the following schedule; Pioglitazone HCL (PIO), EA, CHLOR and HEXA extracts of Urtica piluilifera at two doses of 250 and 500 mg/ kg were used. In addition, a normal control group and a diabetic control one were used for comparison. Blood glucose, insulin resistance, antioxidant enzymes, 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as C-reactive protein and tumor necrosis factor-a levels were evaluated. Results: EA and CHLOR extracts of Urtica pilulifera exhibited a significant hypoglycemia associated with antioxidant and anti-inflammatory effects in diabetic rats; however, HEXA extract showed no beneficial effect. These activities are responsible, at least partly, for improvements that have been seen in hyperglycemia and insulin resistance of diabetic rats. Conclusion: Our results encourage the traditional use of Urtica pilulifera extract as an antioxidant and anti-inflammatory agent as an additional therapy of diabetes. (C) 2012 Elsevier Ireland Ltd. All rights reserved.