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Herbal medicine is the oldest form of healthcare known to mankind and most cultures have long folk medicine histories that include the use of plants. Nephrotoxicity is one of the most common kidney problems and occurs when the body is exposed to a drug or toxin that causes damage to the kidneys. To investigate the Nephroprotective activity of ethanol extract of Plumbago zeylanica on Gentamicin induced Nephrotoxicity in male Wistar rats. In this model of Nephrotoxicity, 30 adult male wistar rats (150-200gms) were evenly divided into 5 groups. Group-1 and Group-2 served as untreated and model controls respectively, while Group-3, 4 and 5 were the treatments groups which were simultaneously treated with standard, 200 and 400 mg/kg extract respectively, after each dose Gentamicin (80 mg/kg, i.p.) for 10 day. On 11th day, blood samples for biochemical parameters, while the rats kidneys for histology were obtained under inhaled diether anaesthesia. Gentamicin treatment caused Nephrotoxicity as evidenced by marked elevation in blood urea, uric acid and Creatinine. Co-administration of extract with Plumbago zeylanica decreased rise in blood urea, uric acid and Creatinine. Apart from these, histopathological changes also showed the protective nature of extract against Gentamicin induced necrotic damage of renal tissues. It was observed that the ethanol extract of conferred nephroprotective activity by histopathological and biochemical observation against Gentamicin induced Nephrotoxicity in rats. In the near future could constitute a lead to discovery of a novel drug for treatment of drug induced Nephrotoxicity.