Introduction: A functional kidney is crucial for human health. The disturbance of kidney functions can progress to acute or chronic renal failure. Chronic renal failure (CRF) is a condition characterized by a progressive loss of kidney function. Pinostrobin) PN) is a dietary bioflavonoid with numerous pharmacological effects, including anti-viral, antioxidant and anti-inflammatory properties. Aim of the Work: The current study sought to clarify molecular, immunohistochemical, and histological changes in the testicles of adult albino rats suffering from chronic renal failure and to show whether or not pinostrobin might reverse these changes. Material and Methods: Three equal groups of thirty adult male albino rats were created: Group I, control group. Group II (CRF): Rats of this group were undergone to unilateral ureteral obstruction. They were followed up for 12 weeks. Group III (CRF+ PN): Rats of this group were undergone to unilateral ureteral obstruction and followed up for 12 weeks, then, they received pinostrobin 40 mg/kg of PN by oral gavage) for 8 weeks). The testes were removed from all groups and processed for histological study. Results: The current study's findings showed that the CRF group's spermatogenic, Sertoli, and Leydig cells had degenerative alterations, which were linked to a statistically significant variation in the germinal epithelial height, area percent of collagen fibers and PCNA immunoexpression. These alterations were noted to be diminished in Group III. Additionally, the CRF group's serum testosterone, FSH, and LH levels significantly decreased before returning to normal following pinostrobin administration. Serum levels of malondialdehyde and total antioxidant capacity (TAC) were also elevated and lowered, respectively. Conclusions: Pinostrobin could protect the testis against the harmful consequences of chronic renal failure. So, it might be an appropriate nutritional supplement to help mitigate some of its drawbacks.