Shigellae are the most frequently isolated invasive bacteria in Djibouti. 140 clinical strains collected during an eight months period have been studied for their in vitro susceptibility to antibiotics mainly used in treatment and prophylaxis by measure of MIC (agar dilution) for all antibiotics except for trimethoprim-sulfamethoxazole, trimethoprim and sulfamethoxazole (disk diffusion on lysed horse blood medium). Characterization of beta-lactamase is carried out for all strains resistant to amoxicillin and for all S. sonnei. The overall prevalence of resistance to amoxicillin is 41.7% (penicillinase TEM-1, OXA-1 and OXA-3 alone or associated) to tetracyclines 97.1% and to trimethoprim-sulfamethoxazole 51.4%. This prevalence is particularly high for amoxicillin with S. flexneri and for trimethoprim-sulfamethoxazole with S. sonnei. All strains of S. sonnei have a low level chromosomal cephalosporinase without phenotypic expression. Among 68 strains sensitive to trimethoprim-sulfamethoxazole, 39 are resistant to sulfamethoxazole alone. All strains are sensitive to nalidixic acid and fluoroquinolones. These data allows us to recommend fluoroquinolones for treatment and prophylaxis of shigellosis in Djibouti.