Abstract: Doxorubicin (DOX), one of the anthracycline antibiotic drugs isolated from the soil fungus Streptomyces peucetius caesius, which has been widely used to treat cancer effectively. It has also been known to induce reproductive abnormalities in males. The implication of natural phenolic compounds in the prevention of many pathologic diseases has been reported. Herein, the ability of polyphenolic-rich Grapefruit Seed Extracts (GSE), to protect rat testis against DOX-induced histomorphometric impairment was investigated. Four groups of Wistar rats were used; The GSE- alone group received intraperitoneal (i.p.) Normal Saline (NS) 2.5 mg kg-1 b.wt. followed by orally GSE 10 mg kg-1 b.wt. daily for 16 weeks. The DOX-alone group were given i.p., DOX 20 mg kg-1 b.wt. as a single dose. The GSE plus DOX-group were similarly given DOX, but also had oral GSE 10 mg kg-1 b.wt. post-treatment for 16 weeks. Another group of rats were each given orally 2.5 mL kg-1 b.wt. peanut oil (vehicle) daily for 16 weeks, after 2.5 mL kg-1 b.wt. normal saline was given as a single dose i.p., to serve as the control. The animals were sacrificed 16 weeks after DOX or NS injections. The testicular toxicity induced by DOX was assessed by histologic and stereologic evaluation of the testis. Present results demonstrated that post-treatment with GSE was capable of reversing the reduction of body and testicular weights as well as the testicular histomorphometric evidences of high dose and delayed DOX toxicity in the animals. The GSE was therefore shown to exert testicular cytorejuvinative effects on rats challenged with DOX.