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At present, penicillin is recommended as the optimal regimen for syphilis, but there are still limitations in its application. In treatment for early syphilis, azithromycin regimen is easy to implement with a good compliance, and its efficacy has been proved by several studies, resulting in recommending this regimen as alternative treatment of early syphilis among those patients who are allergic to penicillin. Meanwhile, azithromycin regimen has its advantage in applying in the field and simultaneously treating co-infection with other sexually transmitted infections. Recently, azithromycin-resistant Treponema pallidum due to gene mutation has occurred, resulting in the treatment failure in early syphilis, and transmitted within sexual network, which has tempered further use of this regimen.