Background: The long term effects of diabetes mellitus include progressive development of the specific complications of nephropathy that may lead to Diabetic nephropathy (DN). The objective of this study was to investigate the development of Diabetes mellitus type 2 (T2D) in Streptozotocinnicotinamide model followed by DN to estimate the Reno-protective effects of an Egyptian Herbal mixture formulation (HMF) consisting of (Panax ginseng, Momordica charantia and Gymnema sylvestre) on diet intake, bodyweight, water consumption, urine output, urine sugar, urine protein, fasting blood glucose, insulin, Glomerular filtration rate, glycosaminoglycans, renal oxidative stress marker malondialdehyde (MDA) in urine, blood and renal tissue of rats. Method: White male albino rats weighing 150-200 gm about 4 month old were used for this study. 10 rats were fed a normal basal diet (Cr), 30 overnight fasted rats were Non insulin dependent diabetes mellitus (NIDDM)-induced by IMI of 60 mg/kg Streptozotocin (STZ) and thereafter 120 mg/kg nicotinamide was injected after 5 min. The rats found with permanent NIDDM were used for anti diabetic study and were equally divided into 2 subgroups each one include 10 rats. The first group with no supplement, the 2nd group received T2D+HMF. HMF was administered at 56 days (start time for treatments) for 8 weeks. Diet intake, bodyweight, water consumption, urine output, urine glucose, urine protein, fasting blood glucose, insulin level, Glomerular filtration rate, renal glycosaminoglycans were measured. Furthermore, renal oxidative stress marker (MDA) and renal enzymes involved in the synthesis/degradation of glycosaminoglycans (L-glutamine fructose-6-phosglucosaminidas-phate aminotransferase, N-acetyl and b-glucuronidase) were analyzed. Results: HMF showed a marked decrease in diabetes induced polydypsia, polyuria, urine sugar, hyperglycaemia, glomerular filtration rate, proteinuria and renal glycosaminoglycans. Increased activities of renal enzymes involved in the synthesis/degradation of glycosaminoglycans (L-glutamine fructose-6-phosphate aminotransferase, N-acetyl glucosaminidase and b-glucuronidase) were significantly lowered by HMF supplementation during diabetes. Glycosaminoglycans and their components (aminosugar, uronic acid) revealed decreasing trends during diabetes and HMF effectively countered this decrease. The increase in renal oxidative stress markers (MDA) was significantly decreased by HMF supplementation during diabetes. Conclusion: STZ induced-diabetes (DM) associated with hypoinsulinemia, renal function disturbances due to imbalance in synthesis/degradation of glycosaminoglycans and defective antioxidant stability that may have implications for the progress of DM and its related problems. Treatment with HMF improved DM and its associated renal problems in different degrees through controlling the level of glycosaminoglycans and oxidative stress during diabetes thus prolonging late complications of diabetes.