We studied an ethyl acetate (EtoAC) extract of leaves obtained from the medicinal and ornamental tree, Lagerstroemia speciosa L, for nephroprotective activity in cisplatin-induced acute renal injury in Balb/C mice. The EtoAC extract at dose levels of 50 and 250 mg/kg showed a dose-dependent reduction in cisplatin-induced elevations in urea and creatinine concentrations. Additionally, treatment with the EtoAC extract prevented the cisplatin-induced decline of the renal antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione. The findings suggest that the EtoAC extract from L. speciosa possesses marked nephroprotective activity and could offer a promising role in the treatment of acute renal injury caused by a nephrotoxin like cisplatin.