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Abstract: Aim of the study: The present study was carried out to isolate and identify trans-tiliroside as principal compound with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinesis. Materials and methods: A bioactive compound, trans-tiliroside was isolated from the ethanol extract of Potentilla chinesis and its administration dose was optimized and patented. The normal, alloxan-induced diabetic mice and streptozotocin-induced diabetic rats were used to evaluate the anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects of trans-tiliroside from Potentilla chinesis. Biochemical parameters were assayed in blood samples of different groups of alloxan-induced diabetic mice and streptozotocin-induced diabetic rats. Results: The level of fasting serum glucose levels, triglycerides (TG) and total cholesterol (TC) in alloxan-induced diabetic mice were significantly decrease after daily oral administration of trans-tiliroside in normal and diabetic mice at doses of 0.4, 0.8 and 1.6mg/kg/day, for 15 days. Blood glucose level was significant decrease in STZ induced diabetic rats by trans-tiliroside (1.2 and 0.3mg/kg body weight for 10 weeks). The content of TC, low density lipoprotein (LDL–C) and TG levels were decreased and high density lipoprotein (HDL–C) content was increased, so lipid metabolism was improved. Moreover, trans-tiliroside revealed antioxidant activity as shown by increased activities of superoxide dismutase (SOD), decreased level of malondialdehyde (MDA) in diabetic rats. Histological morphology examination showed that the trans-tiliroside restored the damage of pancreas tissues in rats with diabetes mellitus. Conclusion: Trans-tiliroside, a constituent from Potentilla chinesis, revealed significant anti-hyperglycemic, anti-hyperlipidemic and antioxidant activities. [Copyright &y& Elsevier]