Cisplatin (CP) is a potent antineoplastic agent that triggers nephrotoxicity as a major adverse effect which can cause treatment interruptions and limitations to its clinical use. Nephrotoxicity associated with CP involves inflammation, oxidative stress, and apoptosis in kidney tubules. The objective of this work was to assess the effect of the blockade of endothelin-1 (ET-1) receptor with ambrisentan on altered renal function induced by CP. Swiss albino mice were assigned into control, CP, CP/Amb-5, and CP/Amb-10 groups. Ambrisentan improved kidney function (serum creatinine and BUN) and histopathological changes in comparison to CP-treated group. Ambrisentan significantly reduced protein expression of p75