Star anise (Illicium verum) has been used in the folk medicine of China, India, and most other Asian countries to treat stomach aches, vomiting, insomnia, dermal inflammation, and rheumatic pain as well as a common spice usage. The present study was designed to investigate the possible ameliorating effect of star anise fruit extract against Etoposideinduced nephrotoxicity in rats to prove the evidence of its traditional pharmacological effectiveness. A total of 40 male Wister albino rats were divided randomly into four groups (1st group was control; 2nd group was treated with star anise, 3rd group was received Etoposide, and 4th group was treated with both star anise and Etoposide. The administration of Etoposide significantly caused elevation in creatinine, blood urea, sodium, potassium, and chloride while calcium ions were significantly decreased when compared with the control group. Co-treated rats with star anise and Etoposide maintained the levels of the measured parameters (creatinine, chloride, and calcium ions) closer to the normal values while urea, sodium, and potassium ions were significantly decreased when compared with the Etoposide group. Histopathological evidence, together with observed Ki67-ir, supported the detrimental effect of Etoposide and the ameliorating effect of star anise water extract on renal toxicity. Finally, it could be concluded that star anise has a promising role and it worth to be considered it as a natural substance for ameliorating the renal toxicity and injury induced by Etoposide chemotherapy.