Abstract: Activities of total flavonoids from Gnaphlium affine D.C. on blood glucose and lipid levels in diabetic mice were studied. Diabetes was induced by intraperitoneal injection of streptozotocin in mice. Changes of body weight, glucose tolerance, glycosylated serum protein (GSP) , liver glycogen, and lipid matabolism in serum of mice were detected. Experimental results showed that the blood glucose and lipid levels disorder of diabetic mice were significantly improved by total flavonoids from Gnaphlium affine D.C. Levels of glucose tolerance, GSP, TG, TC, and LDL-C of total flavonoids from Gnaphlium affine D.C. group were significantly decreased, and levels of liver glycogen and HDL-C significantly increased. In conclusion, total flavonoids from Gnaphlium affine D.C. could effectively ameliorate the blood lipid metabolism of diabetic mice.