The protective and/or therapeutic effect of berberine on cyclophosphamide-induced testicular injury was investigated in rats. A total of 40 male Sprague-Dawley rats were divided into 5 groups (n=8 per group). The control group received saline and CP, BER75, BER150 and BER300 groups received single dose of intraperitoneal 200 mg/kg CP on day 8. Berberine (75 mg/kg, 150 mg/kg and 300 mg/kg) was administered orally for 7 days before and after the CP injection. At the end of the protocol, testes were removed for histological examination, immunohistochemical staining, and biochemical assessments. In our study, CP did not cause a significant change in body weight and testis weight, whereas berberine treatment significantly decreased body weight. Although no significant change was observed in terms of oxidative stress markers and cytokine levels, degenerative changes and apoptotic findings were found in the CP group; which were improved significantly with increasing doses of berberine treatment. In conclusion, we found that treatment with berberine may have anti-degenerative and anti-apoptotic potential rather than altering oxidative stress markers and/or inflammatory pathways in CP-induced testicular damage.