Objectives: The aim of this study was to examine the ultra-structure of the dentin-adhesive interface after artificial secondary caries formation around two-step self-etching primer adhesive systems by a SEM. Methods: Dentin disks obtained from human molars were ground with #600-grit SiC. Either Clearfil SE Bond (SE, Kuraray Medical), Clearfil Protect Bond (PB, Kuraray Medical), Unifil Bond (UB, GC) or MacBond II (MB, Tokuyama Dental) was applied to the dentin surface according to the manufactures' instructions. A flowable resin composite (Metafil Flo, Sun Medical) was put between two prepared specimens and light-cured for 40 sec to make a dentin disk sandwich. Specimens were then subjected to the following acid-base challenge; each specimen was then stored in a buffered demineralizing solution (pH 4.5) for 90 min to create artificial secondary caries. The specimens were then immersed in 5% NaClO for 20 min to remove the demineralized dentin collagen fibers. Following this, Super Bond C&B (Sun Medical) was applied on the surface. The specimens were then vertically sectioned and polished with diamond pastes down to 0.25 μm. The polished surfaces were etched with argon-ion beam (EIS-IE, Elionix, Japan) for 40 sec and observed by a SEM (JSM-5310LV, JOEL, Japan). Results: For all the groups, bonding resins resisted against the acid-base challenge, and also the acid-base resistant zone (ABRZ) was clearly observed adjacent to the hybrid layer. However, for UB and MB, the ABRZ was thinner compared with SE and PB. Conclusions: The self-etching primer systems indicated good resistance against the artificial secondary caries formation. However, the ultra-structures around the dentin-adhesive interface after acid-base challenge were material dependent.