Renal Ischemia/Reperfusion (I/R) injury is one of the common factors contributing to acute kidney injury (AKI), which is brought on by a rapid, and sudden stoppage of blood flow followed by a massive influx of blood, and reoxygenation. Methods: This study is designed to evaluate the potential renal protective effect of PRP and exosome injection before the reperfusion phase on the kidney following renal I/R injury by assessing the histopathological, and biochemical alternations in kidney tissue. Forty mature male Sprague-–Dawley rats were utilized furthermore, subdivided into control, I/R, PRP, exosome, and PRP+Ex. The left renal cortex and medulla were processed from all groups for histological examination, and biochemical evaluations of serum Na, K, urine creatinine, and urea were performed. Results: Our finding proved that PRP injection restored normal renal histomorphology. Significant enhancement in serum and urine indicators relates to kidney functions. Conclusions: We concluded that the injection of PRP before the reperfusion phase exerts a significantly superior effect on the kidney following the renal I/R injury model.