Introduction: Chloroquine phosphate (CQP) and hydroxychloroquine sulfate (HCS) are antimalarial drugs commonly used for treatment of malaria and numerous rheumatic diseases. Their widespread prescriptions may accompany with prolonged duration of therapy and higher daily dosages, leading to several toxic effects, including disturbance of reproductive system. Aim of the study: The present study was designed to compare the effect of six-week exposure to CQP and HCS on reproductive function of adult male albino rats. Materials and Methods: The study was conducted on 30 normal adult male albino rats divided equally into 3 groups (10 rats each), the Control-group (C-group) was given 1 ml of distilled water orally, whereas the CQPgroup (62 mg/kg/b. wt. ) and HCS-group (124 mg/kg/b. wt. ) were given single daily oral doses equivalent to 1/10th of LD50 of each drug for 6 consecutive weeks then all animals sacrificed. The serum levels of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH), quality of epididymal sperm (count, motility, viability, and morphology), degeneration severity of seminiferous tubules (SNT) and Leydig cells count per each animal, semi-quantitative scoring of SNT and Leydig cells histopathological changes, spermatogenesis maturity levels, and structural and ultrastructural morphologies of tissues were estimated. Results: The CQP-group showed severe orchidotoxic effects as manifested by statistically significant reductions in final weight gains of body, testes, and epididymis, all sperm quality, and all hormone levels, marked increases in the number of animals associated with SNT degeneration and reduced Leydig cells count, statistically significant increases in abnormalities of SNT and Leydig cells architectures, statistically significant decrease of spermatogenesis maturity levels, and extensive structural and ultrastructural changes in testicular parenchyma and interstitial tissues as compared to C-group and HCS-group. While, HCS-group displayed minor orchidotoxic effects as evidenced by insignificant changes in most of the evaluated parameters, significant reductions of LH and FSH levels, slight increases in the number of animals accompanied with SNT degeneration and reduced Leydig cells count, and minor changes of structural and ultrastructural testicular tissue architectures as compared to C-group. Conclusion, these results suggest that CQP has more orchidotoxic effects than HCS, and in terms of therapeutic usage, physicians should better prescribe HCS as it appears safer than CQP. Also, assessment of male reproductive functions should be done periodically for patients receiving both drugs for prolonged time, especially CQP, as they may induce endocrine disruptions.