Cyclosporine A (CsA) is a potent immunosuppressive drug, it is commonly used to treat rheumatoid arthritis and polymyositis; however, treatment with CsA develops nephrotoxicity. Natural plants are perfect remedies as they cost less, and they are easier to obtain without any troubles. Date fruit is utilized as a main food in the Gulf region. Date pits are the spin-off product of dates through industrial processing. They have antioxidative activity. This research aimed at assessing the impact of date pits’ aqueous extract (DPE) on CsA- induced nephrotoxicity. Male rats (=40) were classified to 4 groups. (I): control negative; (II) CsA: rats injected subcutaneously (SC) with CsA at a dose of (15 mg/kg( for 28 d: (III &IV): DPE + CsA: rats which received DPE orally at a dose of 4 and 6 ml/kg/d, respectively and recieved SC CsA through injection. After 28 d, the rats were sacrificed, and the blood samples were collected. Serum creatinine, urea, uric acid, sodium were measured. The concentration of both lipid peroxidation product (malondialdehyde) and reduced glutathione as well as catalase enzyme activity were determined in kidney tissues. Also, the renal tissues from rats in different groups were examined using light microscope. The results showed that CsA injection induced significant increase in the kidney functions, total protein and ionic potassium, with a significant decrease in albumin, ionic sodium, as well, it induced oxidative stress compared with the control group (P<0.05). The administrated DPE either at low or high dose induced a significant amelioration (p<0.05) in tested parameters compared to CsA values. Furthermore, it protected against CsA-induced histopathological changes. The high dose was the most effective dose compared with the low dose. The results of this study revealed that DPE attenuated CsA-induced nephrotoxicity via an antioxidant mechanism.