Cyclosporine (CSP) is the drug most commonly used for organ transplants, which has immunosuppressive effect, concomitant with development of renal toxicity. Ziziphusspina-christi leaves extract (ZSCLE) has been tested to be an excellent antioxidant, thereby can play a role in the treatment of renal toxicity. The study was conducted to examine the effect of ZSCLE on CSP-induced kidney damage. Forty male albino rats have been distributed into four groups. Group I (Con); rats received distilled water for 2 weeks then intraperitoneal (i.p) injected with olive oil (vehicle) for 21 days. Group II (CSP); rats received distilled water for 2 weeks then were i.p. injected with CSP at a dose (25 mg/kg b.wt) diluted in olive oil for a peroid of twenty one days. Group III ZSCLE (300 mg/kg) + CSP. Group IVZSCLE (600 mg/kg)+ CSP. Rats in groups III and IV received ZSCLE orally for twenty one days, followed by i.p. injected with CSP. Blood was collected for biochemical analysis. The kidney was also examined histopathologically. The results of the study illustrated that CSP induced significant increase in serum levels of kidneys function (serum levels of creatinine (Cr), uric acid (UA) and blood urea nitrogen), serum ionic potassim (K(+)level and the renal lipid peroxides (MDA), but there were decreased in levels of serum ionic sodium (Na+) and renal superoxide dismutase (SOD) compared to Con group. Renal tisuues shows congestion, thickening of renal capsule and coagulated necrosis of epithelial lining in the CSP group. Oral adminstration of ZSCLE at doses of three hundred and six hundred mg/kg/day significantly ameliorated CSP- induced renal oxidative stress. It reduced CSP-induced elevation in serum kidney function parameters, as well as the changes in ionic Na+ and K(+ )levels compared with CSP group. It also protected against CSP-induced histopathological changes.