Nickel (Ni) is a widely distributed metallic environmental pollutant and reported to be the highest potential risk to health of populations. This work aimed to investigate the ameliorative effect of curcumin (80 mg/kg. b.w. P.O. every other day) and/or zinc (227mg/L in D.W.) against NiCl2 (1200 ppm (Ni) in D.W.)- induced nephrotoxicity in rats. One hundred and twenty female albino rats were used. They were divided into two main groups (A &B) 60 rats each. Each group was subdivided into sex subgroups, 10 rats each. Group A (administrated the antioxidants concomitantly with nickel for 8 weeks), group B (administered the antioxidants 2 weeks prior to nickel exposure and 8 weeks with nickel). Subgroup A1& B1 (Normal control), A2 & B2 (Control +ve), A3 & B3 (Ni + corn oil), A4 & B4 (Ni + curcumin), A5 & B5 (Ni + zinc) and A6 & B6 (Ni + curcumin + zinc). NiCl2- exposed rats showed significant elevation in serum urea, creatinine levels and serum, renal MDA levels and CAT activities. Moreover, NiCl2 exposure induced significant decrease in serum and renal GSH levels. Furthermore, histopathological examination of renal tissues showed necrobiotic changes in renal tubules with hypercellularity of glomeruli. Treatment (concomitantly with Ni) and pre-treatment (Pre- Ni exposure) with curcumin and/or zinc improved the altered biochemical parameters and renal histopathological changes. In conclusion, curcumin and or/zinc administration reversed NiCl2-induced nephrotoxicity in rats via their ameliorating antioxidant effects. Pre-treatment with curcumin and zinc combination provided the greatest protection.