Aim: To observe the preventive and therapeutic effects of Ginkgo biloba extract (GbE) on early experimental diabetic nephropathy (DN) in rats.Methods: After an early DN model was induced by streptozotocin, rats were administered GbE at 3 doses for 12 weeks. Fasting blood glucose, creatinine (Cr), blood urea nitrogen (BUN), urine protein, kidney index, anti-oxidase, advanced glycosylation end prod- ucts (AGE), collagen Ⅳ and laminin, matrix metalloproteinases-2 (MMP-2) and the tissue inhibitor of metalloproteinase-2 (TIMP-2), connective tissue growth factor (CTGF), and transforming growth factor-[β1 (TGF-β1) mRNA were measured by different methods. The ultrastructural morphology and the thickness of glomeru- lar base membrane (GBM) were observed by a transmission electron microscope.Results: For the GbE-treated DN rats, when compared with the vehicle-treated DN rats, the fasting blood glucose level, Cr, BUN, urine protein level, and the intensity of oxidative stress were significantly decreased. The expression of MMP-2 greatly increased, and TIMP-2 decreased. Also, AGE, either in serum or in renal,the collagen IV, laminin, CTGF levels, and TGF-β1 mRNA were reduced. Furthermore, both relative grades of mesangium hyperplasia by microscopical observation and the thickness of GBM by electron microscope measurement de-creased significantly.Conclusion: GbE has protective effects on several pharma-cological targets in the progress of DN and is a potential drug for the prevention of early DN.