Objectives: This study was designed to evaluate the ability of two experimental Zn-doped-adhesive (zinc chloride and zinc oxide nanoparticles) alone or with calcium phosphate nanoparticles to induce therapeutic effect on the bonded resin-dentin interface using two adhesive systems(total etch and self-etch). Material and Method: eighty human premolar dentin surfaces were assigned into four main groups (n=20) according to zinc doping (A1), the universal single bond doped with zinc chloride (ZnCl2), (A2) the universal single bond doped with zinc oxide nanoparticles (NZnO), (A3) the universal single bond doped with zinc chloride +calcium phosphate nanoparticles (NACP) (A4) the universal single bond (as a control). Each group was further subdivided into tow subgroups according to the adhesive technique either etch and rinse (B1) or self-etch (B2). Prepared samples were stored in distilled water for 24h, and then submitted to microtensile bond strength testing. Two samples from each group were prepared for observation of nanoleakage by the scanning electron
microscope (SEM). Data was collected and statistically analyzed. Results: In the total etch adhesive technique, the highest mean value was recorded in group(A4 B1), followed by (A2B1) and (A3B1) groups; with the least mean value for the (A1B1) group. Using the self-etch adhesive technique, the highest mean value was recorded in the (A2B2) and (A4B2) groups followed by (A3B2) group with the least mean value for (A1B2) group. Comparing the adhesive techniques, there was statistically significant difference with higher mean value for the etch and rinse adhesive technique except with NZnO group. Conclusion: Addition of zinc to the universal single bond significantly affected the microtensile bond strength except with ZnO nanoparticles group in the self-etch adhesive technique.