ObjectiveTo evaluate clinical efficacy of benzylpenicillin combined with longacting antimicrobial agent in treating hard chancre. Methods130 cases of primary syphilis with hard chancre were randomly divided  into two groups. Patients were all treated with benzylpenicillin as recommended for primary syphilis in Clinical Guideline of Diagnosis and Treatment of SexuallyTransmitted Diseases issued by Chinese Center for Disease Control and Prevention. In addition to the use of benzylpenicillin, topic longacting antimicrobial agent was applied to the lesions in the experimental group. The healing time of the lesions and disease progression were observed at followups on day 7, 11, 15, and 20 of  treatment, rapidplasmareagin test (RPR) was checked on day 60.ResultsHealing time of the hard chancre in the experimental group was obviously shorter than that of  control group. The healing rate of hard chancre skin rash on day 7,11 and 15 was 57.58%, 80.30%  and 100.00% respectively in experimental group, and was 37.50%, 59.38% and 89.06% respectively in control group, there was significant difference in two groups (all P＜0.05);  The results of RPR test at 2month followup and longterm observation on the secondary syphilis showed no significant difference(P>0.05).ConclusionBenzylpenicillin in combination with longacting antimicrobial agent can shorten healing time of lesions of hard chancre and reduce transmission of Treponema pallidum.