Objective: To investigate the hormonal, histopathological toxicity and sperm quality of ciprofloxacin in male genital system in the rabbit model. Methods: Twenty adult New Zealand male rabbits were randomly divided into the treatment and control groups, and respectively received 30 mg/kg/day ciprofloxacin and normal saline intraperitoneally for 14 days. Blood samples and testicular tissues were taken for testosterone by enzyme linked immunosorbent assay method, and measurement of histopathologic and histomorphometric investigations was made on the 14th day of the experiment and 56 days after the last dose of ciprofloxacin. Additionally, epididymis sperm sample was collected for quality analysis. Results: On day 14 of the experiment, histopathologic examination revealed severe degenerative changes in the epithelium of seminiferous tubules and loss of all germ cells in most tubes in the treatment group. In the histomorphometric study, significant reductions in the seminiferous tubules diameter, epithelium height, and Johnsen’ score were observed. On day 56 after the last dose of ciprofloxacin, the seminiferous tubules revealed regeneration in the treatment group and no significant difference was observed in the spermatogenesis parameters except epithelial height parameter between the control group and the treatment group. All sperm quality parameters were significantly decreased on day 56 after the last dose of ciprofloxacin. Testosterone levels did not significantly change during the follow-ups period. Conclusions: There is potential reversible testicular toxicity for ciprofloxacin in the rabbit model in according to relative regeneration of spermatogenic epithelium after 56 days of last dose of ciprofloxacin. Sperm quality will be improved with a delay after complete regeneration of seminiferous tubules.