The effects of polydeoxyribonucleotide (PDRN), an agonist of the A2A adenosine receptors which when activated positively influences sperm activity, were tested in an experimental testicular ischaemia ⁄ reperfusion injury model. Anaesthetized male Sprague-Dawley rats were subjected to testicular torsion-induced ischaemia, followed by reperfusion (TI ⁄ R). Immediately after detorsion, randomized animals, including SHAM, received intraperitoneal injections of: (i)vehicle (1 mL⁄ kg 0.9% NaCl solution); (ii) PDRN (8 mg⁄ kg); (iii) DMPX (3,7-dimethyl-1-propargilxanthine, 0.1 mg⁄ kg); or (iv) PDRN (8 mg⁄ kg) +DMPX (0.1 mg⁄ kg). Animals were euthanized at 1, 7 and 30 days following reperfusion. Vascular endothelial growth factor (VEGF) expression is normally associated with adenosine A2A receptor stimulation. After treatment, VEGFmRNA⁄ protein expression quantified by qPCR and Western blot, vascular endothelial growth factor receptor-1 (VEGFR1) and endothelial nitric oxide synthase (eNOS) mRNA measured by qPCR, VEGF and VEGFR1 assessed using immunohistochemical methods, histological staining and spermatogenic activity were all analysed. Testis ischaemia-reperfusion (TI ⁄ R) injury caused increases in VEGF mRNA and protein, VEGFR1 and eNOS mRNA, histological damage and reduced spermatogenic activity. Immunostaining showed a lower expression of VEGF in germinal epithelial cells and a strong expression of VEGFR1 in Leydig cells after TI ⁄ R. PDRN administration increased significantly VEGF message ⁄ protein, VEGFR1 and eNOS message, decreased histological damage and ameliorated spermatogenic activity. PDRN might be useful in the management of testicular torsion.