Diabetes mellitus (DM) and neurosyphilis (NS) may both damage the blood-brain barrier (BBB). It seems that non-neurosyphilis (non-NS) patients with high HbA levels are likely to develop into NS. However, the correlation of HbA level with BBB disruption in syphilis (non-NS) patients is unclear. In this study, we used dynamic contrast-enhanced (DCE) MRI to quantify regional BBB permeability in syphilis (non-NS) patients and detected several molecular biomarkers of cerebrospinal fluid (CSF). We found that BBB permeability values in the hippocampus, white matter, and cortex inferior temporal gyrus were correlated with albumin quotient (Qalb), CSF concentrations of interleukin IL-6 and IL-10. Moreover, BBB breakdown in white matter was correlated with CSF concentrations of sICAM-1 and sVCAM-1. In conclusion, our data suggest that BBB integrity may be liable to be disrupted in syphilis (non-NS) patients, patients with high HbA levels, as well as syphilis (non-NS) patients with high HbA levels, and it is particularly important to control blood glucose in these patients.