To investigate the role of the Fas/Fas ligand (Fas/FasL) system in testicular toxicity induced by epirubicin (Epi) and to correlate the system with the serum levels of soluble Fas and Fas ligand (sFas/sFasL), epirubicin was intraperitoneally administered to male Sprague-Dawley male rats at doses of 1.2mg/kg once a week for 10 weeks, and genital organ weights and histopathology were examined. Fas and FasL expression in rat testis were examined by immunohistochemistry. Apoptosis was assessed by TUNEL assay. Expression levels of Fas and FasL were analyzed by RT-PCR and Western blotting. Serum sFas/sFasL levels were determined by ELISA. The results show that the testicular toxicity of Epi involved germ cell apoptosis. Fas and FasL protein expression levels were markedly increased in Epi-treated rat testes, as was expression of sFasL. In particular, increasing serum sFasL levels were positively correlated with elevated expression levels of FasL and sFasL in the testes of Epi-treated rats, revealing serum sFasL to be a promising marker of testicular toxicity after cytotoxic chemotherapy.