OBJECTIVE The current study focused on the pro-fertility potential of Senecio biafrae (Sb) extract and vitamin C in Male Sprague Dawley (SD) rats with tetracycline-induced infertility. METHODS A total of 36 male and 36 female adult SD rats were used for this investigation. The male rats randomly assigned to Group A (controls) were given normal saline 2ml/kg. Rats in Groups B, C, D, E, and F were respectively administered [30 mg/kg of body weight (bwt) of tetracycline], [30 mg/kg bwt of tetracycline + 50 mg/kg of vitamin C], [30 mg/kg bwt of tetracycline + 500 mg/kg bwt of Sb], [30 mg/kg bwt of tetracycline + 50 mg/kg of vitamin C + 500 mg/kg bwt of Sb], and [30 mg/kg bwt of tetracycline reversal] daily for 28 days via gastric gavage. Tested parameters included sperm parameters, hormonal profile, histology, and fertility test. RESULTS Significant (p<0.05) increases were seen in sperm quality, hormone profile, organ and body weights of the groups treated with vitamin C, Sb, and tetracycline. There was derangement in sperm quality, hormone profile, and organ and body weight of the animals in group B. Histoarchtecture of the testes showed normal cellular composition in the germinal epithelium with sperm cells in the lumen and normal interstitium in groups A, C, D, and E. Group F showed abnormal spermatogenesis and poor association of spermatogenic cells, however there was depletion in the seminiferous epithelium in the group treated with tetracycline. CONCLUSIONS Senecio biafrae defeated the deleterious effects of tetracycline on the male reproductive system of rats treated with the drug.