This work investigated the effect of N-acetylcysteine (NAC), on renal hemodynamics in cisplatin (CP)-induced nephrotoxicity in Wistar–Kyoto (WKY) rats. The animals were divided into four groups (n = 5 or 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) N-acetylcysteine (500 mg kg−1 per day for 9 days), respectively. The third and fourth groups were given a single intraperitoneal (i.p.) injection of CP (5 mg kg−1) and an i.p. injection of CP (5 mg kg−1) together with i.p. NAC (500 mg kg−1 per day for 9 days), respectively. At the end of the experiment, rats were anesthetized and blood pressure and renal blood flow were monitored, followed by intravenous (i.v.) injection of norepinephrine (NE) for measurement of renal vasoconstrictor responses. CP caused a significant reduction in renal blood flow but did not affect NE-induced renal vasoconstriction. In addition, CP significantly increased plasma concentrations of urea and creatinine and urinary N-acetyl-β-D-glucosaminidase (NAG) activity and kidney relative weight. CP decreased body weight and creatinine clearance. Histopathologically, CP caused remarkable renal damage compared with control. NAC alone did not produce any significant change in any of the variables measured. However, NAC significantly ameliorated CP-induced hemodynamic, biochemical and histopathological changes. The concentration of platinum in the kidneys of CP ? NAC treated rats was less than in CP-treated rats by 37%. The results show that administration of i.p. NAC (500 mg kg−1 per day for 9 days) reversed the renal hemodynamic changes as well as the biochemical and histopathological indices of CP-induced nephrotoxicity in WKY rats. Copyright © 2009 John Wiley & Sons, Ltd.