Doxorubicin (DXR) is used against the cancer but it has some adverse effects (gonadotoxicity, cardiotoxicity and nephrotoxicity). We aimed to determine the effect of DXR toxicity on reproduction and whether Darbepoetin (DP) and Ramipril (RAM) treatments play a protective role against this toxicity in male rats. Herein, adult male Sprague-Dawley rats (n=34) were divided randomly into five groups, as control (Group I; n=7, no medication) and four treatment groups (II to V). DXR was administered to all treatment groups (DXR, 2.5 mg/kg/w i.v. for 3 weeks) and they were Group II (DXR, n=6), Group III (n=7, DP 10 μg/kg/w i.p. for three weeks), Group IV (n=7, RAM 1 mg/kg/d p.o. for four weeks), and Group V (n=7, DP+RAM). Rats in all groups were sacrificed after four weeks of treatment. Spermatological parameters along with histopathological images and malondialdehyde levels of testicular tissue were evaluated. Weights of body, testicles, cauda epididymis and male accessory glands in DXR-treated groups were significantly different (P<0.05) from the control group. DXR toxicity adversely altered all the sperm parameters. But, DP plus RAM treatment in Group V improved the DXR-depressed motility and viable sperm rate. Sperm concentrations significantly decreased (P<0.05) in DXR-treated groups as compared to control group. In Group III and V, the increase in total abnormal sperm rate caused by the DXR injections was prevented. In conclusion, this study indicated that weekly DXR injections in adult rats depressed all the epididymal sperm parameters. Co-treatment by DP and RAM protected the sperm cells against the toxicity due to the DXR administration while single usages of the DP or RAM provided partial improvements.