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Background: Brucellosis is one of the most common bacterial zoonotic infections in the world. The incidence of this infection is quite high and is endemic in several countries. According to WHO report, the prevalence of zoonotic and human brucellosis is on the rise in the Mediterranean region, the Middle East, and west Asian countries. The aim of this study was to investigate the usage of silver nanoparticles in treatment of brucellosis. Materials and Methods: In this experimental study, the activity of silver nanoparticles against Brucella meltensis 16M was determined by agar well diffusion method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of silver nanoparticles were determined by macrodilution method. Also, the antibacterial effect of silver nanoparticles was studied in mouse model. Results: The results showed that silver nanoparticles in low concentrations can kill Brucella melitensis 16M in laboratory conditions. MIC and MBC of silver nanoparticles were 4 ppm and 6 ppm in macrodilution method, respectively. The anti-brucella effect of silver nanoparticles was also observed in mouse model. Conclusion: This study demonstrated that silver nanoparticles can be used against brucellosis.