Abstract: Angelica acutiloba root, a Japanese species of Dong quai being cultivated in Hualien County in eastern Taiwan, is used primarily for gynecological disorders in women. Increasing evidence indicates that advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic nephropathy. We investigated whether A. acutiloba root is beneficial in the amelioration of AGE-mediated renal injury in a diabetic rat model. Streptozotocin (STZ)-diabetic rats were treated orally with A. acutiloba root extract (AARE) [50, 100, 200 mg/(kg × day)] for 8 wk. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for enzyme immunoassay, pathology histology, immunohistochemistry, and Western blot analyses. Polyphenolic compounds and flavonoids were abundant in AARE. AARE [200 mg/(kg × day)] partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-h urinary albumin excretion rate, creatinine clearance, and glomerular mesangial matrix expansion were ameliorated by AARE treatment. The increased expression of nuclear factor-κB, transforming growth factor-β1, and the progressive accumulation of fibronectin in kidney of diabetic rats were attenuated by AARE treatment. AARE treatment ameliorated the elevated levels of advanced glycation end products (AGEs) and mitochondrial thiobarbituric acid-reactive substance, as well as the elevated levels of Nɛ-(carboxymethyl)lysine and receptors for AGEs in kidneys of diabetic rats. The results show that A. acutiloba root has an anti-diabetic property that involves antihyperglycemia accompanied by amelioration of glycation-mediated renal damage.