Background: cisplatin is an antineoplastic drug with well known nephrotoxicity, meanwhile Salicylate was recently shown to provide protection against cisplatin nephrotoxicity in rats. Objective: to investigate the possibility to decrease the nephrotoxic effect of cisplatin by Salicylate. Methodology: a total of 120 rats were divided into four groups: the first group was given 20 mg/kg cisplatin, the second was given 20mg/kg cisplatin and sodium salicylate 100mg/kg, the third was given salicylate 100mg/kg and the fourth was given saline and used as control. Biochemical and histopathological changes, DNA fragmentation and tumor necrosis factor-α (TNF-a) were investigated. The effects of cisplatin and salicylate on TNF-a expression, and apoptosis were determined in renal proximal tubular cells of rats. Results: Salicylate significantly reduced both the functional and histological evidence of cisplatin renal injury. Cisplatin increased the renal expression of TNF-a while concomitant administration of cisplatin with salicylate reduced serum TNF-a protein levels. Conclusion: salicylate reduce cisplatin-induced nephrotoxicity as a result of inhibiting TNF-a production. Thus, further experimental and clinical studies on preparations of this combination are warranted.