OBJECTIVE: To determine the efficacy of a fermented buckwheat flower and leaf extract(EFBFL) for the reduction of blood glucose and lipid dysregulation in spontaneously obese type 2 diabetic db/db mice, and to explore the possible mechanisms involved.METHODS: Forty 9-week-old male db/db mice were randomly allocated to a high-dose EFBFL group(EFBFL-H), a low-dose EFBFL group(EFBFL-L),a metformin hydrochloride positive control group(MEG), and a db/db control group(MG), and there was also a db/m negative control group(NCG)(n =10). Oral glucose tolerance tests(OGTT) were performed after 7 weeks of treatment. At the end of 8 weeks of treatment, random blood glucose(RBG),glycosylated hemoglobin(Hb Alc), fasting plasma glucose(FPG), fasting serum insulin(FINS), triglyceride(TG), serum total cholesterol(TC), free fatty acids(FFA), high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol(LDL-c) were measured, the homeostasis model assessment-insulin resistance(HOMA-IR) was calculated. Immunohistochemistry and western blotting measured the expression of glucose transporter4(GLUT4) and peroxisome proliferator-activated receptor γ(PPAR-γ) by in skeletal muscle.RESULTS: The MG mice had a significantly increased in RBG, Hb Alc, the HOMA-IR level, the serum of TG, TC, LDL-c, but a decreased in glucose tolerance and the protein expression of GLUT4 and PPAR-γ compared with the NCG. Compared with the MG, EFBFL groups significantly decreased RBG, Hb Alc, and the HOMA-IR level, increased glucose tolerance. Meanwhile EFBFL groups reduced the serum TG, TC, and LDL-c in a dose-dependent manner. In addition, EFBFL increased the protein expression of GLUT4 and PPAR-γ in the skeletal muscle of db/db mice.There was significant difference between the MG group and EFBFL groups.CONCLUSION: These findings suggest that EFBFL has anti-diabetic effects in db/db mice, ameliorating glucose intolerance, lipid dysregulation, and insulin resistance.