Objective: To determine the seroprevalence of syphilis among blood donors in a Rural Health Zone in north-eastern DR Congo (Isangi). Methods: Cross-sectional study conducted in the Rural Health Zone of Isangi from January 1st, 2010 to December 31st, 2017 involving 814 blood donors. Results: 814 blood donors were counted including 725 males (89%) and 89 females (11%), a sex ratio M / F of 8.14. The majority of blood donors were 17-25 years old (44%) and 25-35 years old (32%) with a mean age of 32.3 ± 8 years. Family blood donors were the majority (90%). The seroprevalence of syphilis was 1.7%. This seroprevalence was higher among young, male, living alone, family, illiterate and primary and non-professional blood donors. No epidemiological parameters studied were significantly associated with the seropositivity of the antibodies sought. Conclusion: The seroprevalence of syphilis was low in blood donors in the Rural Health Zone of Isangi. This seroprevalence would be underestimated because of the use of a single rapid diagnostic test (RPR) in screening blood donors. The improvement of transfusion safety in the Rural Health Zone of Isangi should be directed towards the abandonment of the family donation, the promotion of the voluntary donation, the organization of the donors in "clubs" and their loyalty.