The current study was carried out to evaluate the protective effect of grape seed proanthocyanidins extract (GSPE) against Ehrlich solid tumor (EST) induced renal injury, with the respect to DNA fragmentation and P53 and PCNA proteins expression in renal tissue. A total of 50 female mice were randomly assigned into five groups. Control mice were injected with physiological saline solution. Mice of the 2^nd group were administered with GSPE (50 mg/kg bw/every 2day/per OS) for 2 weeks and injected with physiological saline solution. Mice of the 3^rd group were injected subcutaneously with 2.5 million cells of EAC/mouse. Mice of the 4^th group were injected with EAC as the 3^rd group and administered with GSPE as the 2^nd group simultaneously for 2 weeks. Mice of the 5^th group were injected with EAC as the 3^rd group and left for 2 weeks (till development of solid tumor), then treated with GSPE for another 2 weeks. EST significantly increased serum levels of urea, creatinine, potassium and chloride. In addition, it induced renal tissue and DNA injuries and increased P53, PCNA and ki67 proteins expression in renal tissues. On the other hand, it decreased serum levels of sodium and calcium ions. However, treatment of EST bearing mice with GSPE normalized serum levels of the above-mentioned parameters and improved renal tissue structure and reduced renal tissue DNA damage and P53, PCNA and ki67 proteins expression. These results indicated that GSPE is a promising nephron protective agent against EST induced renal injury.