n a trial to study the possible prophylactic role of vitamin C and fish oil against the cisplatin induced nephrotoxicity in dogs. Forty two dogs were used, classified into seven equal groups. (I) served as control injected with physiological saline, (II) injected with single dose of vitamin C ( 200 mg / Kg b. wt. i. v. ), (III) injected with a single dose of fish oil ( 2 ml / Kg b. wt. i. v. ), (IV) injected with a single dose of cisplatin ( 5 mg / Kg b. wt. i. v. ), (V) injected with a single dose of cisplatin plus vitamin C, (VI) injected with a single dose of cisplatin plus fish oil and (VII) injected with a single dose of cisplatin plus both vitamin C and fish oil. Dogs were sacrificed 7 – days post treatment. Blood samples and kidney tissues were taken for biochemical investigations. from the obtained results, significant decreases were reported in the renal enzyme activities of catalase (CAT), glutathione peroxidase (GpX) and superoxide dismutase ( SOD) and reduced glutathione in cisplatin – injected dogs. In the opposite, plasma and kidney malondialdehyde (MDA), urea (BUM) and creatinine were significantly increased. Administration of vitamin C and / orfish oil concomitantly with cisplatin inhibited the increasein lipid peroxidation and inhibited renal antioxidant enzymes depletion induced by cisplatin. In conclusion, the bi – use of vitamin C beside fish oil during treatment with cisplatin improved the antioxidant defense system and producted an excellent prophylactic role against cisplatin induced nephrotoxicity.