Description: Brucellosis is considered as a major endemic disease in Syria. There is a paucity of data regarding suitable antibiotic prophylaxis. BALB/c mice were challenged with either a low (104 CFU) or a high (107 CFU) concentration of Brucella melitensis. Antibiotics were administrated prior to, post or at the same time as the bacterial challenge. Mice were killed either 48 hours or 30 days after the last injection of antibiotics. Efficacy of antibiotics to limit or control infection was determined by reduced bacterial burden in mice spleens. When a low concentration was injected, sparfloxacin, levofloxacin and doxycycline were effective 48 hours after the cessation of treatment. Sparfloxacin protection was observed 30 days after the cessation of treatment. After a high injected concentration, antibiotics were effective 48 h after the cessation of treatment just in prior to exposure groups. Only sparfloxacin was effective 30 days after the cessation of treatment in prior to exposure group. In conclusion, these results suggest that sparfloxacin and levofloxacin have almost the same protective efficacy as doxycycline against a low concentration of B. melitensis infections