Although a number of animal experiments and clinical trials have investigated the effects of ginseng roots on diabetes, the relationship between its therapeutic effects on diabetes and the quality and the growth age of this herb have not yet been reported.This study systematically investigated the effects of 3-to 6-y-old ginseng roots on glycemic and plasma lipid control in a rat model of type 2 diabetes.Six groups of male Goto-Kakizaki (GK) rats received either metformin, 3-to 6-y-old ginseng root, or no treatment.The treatments were administered twice daily for 9 weeks.A combined approach was used that involved applying liquid chromatography-mass spectrometry-based lipidomics, measuring biochemical parameters and profiling the components of ginseng roots of different ages.Compared to the untreated controls, treatment with 4-and 6-y-old ginseng roots significantly improved glucose disposal, and 5-y-old ginseng treatment significantly increased high density lipoprotein cholesterol.Treatment with 6-y-old ginseng significantly decreased total plasma triacylglyceride (TG) and very-low-density lipoprotein cholesterol and improved plasma glycated hemoglobin (HbAlc).In addition, treatment with 4-to 6-y-old ginseng influenced plasma lipidomics in diabetic GK rats by reducing TG lipid species.Metformin significantly reduced fasting blood glucose by 41% and reduced HbAlc by 11%, but showed no effects on the plasma lipid parameters.