Purpose: This study investigated the microshear bond strength (MSBS) of resin composite to artificially demineralized enamel and dentin treated with casein phosphopeptide amorphous calcium phosphate (CPP-ACP), using two adhesive systems (Etch & Rinse and self etch adhesives) for two time periods (1 month and 3 months). Materials and Methods: CPP–ACP was used as a Remineralizing agent, Resin composite Filtek Z350(nano-filled) and two types of adhesive systems Adper Single Bond Plus(Etch&Rinse adhesive) and Single Bond adhesive(Self-etch adhesive),were selected. Eighty human molars were used. The samples were divided into two main groups, 40 teeth each, according to tooth substrate, either Enamel or Dentin, each group was further subdivided into two equal subgroups according to the type of adhesive system, either etch& rinse or self-etch adhesive system . Each subgroup was further subdivided into two classes of 10 specimens each according to the storage period either one or three months. For enamel testing, Buccal enamel surfaces were embedded in self cure acrylic resin using specially designed Teflon mold. For dentin testing, all occlusal enamel was removed to expose flat dentin surface. Enamel and dentin specimens were artificially demineralized and remineralized using CPP-ACP crème. Composite specimens were made using Intravenous pediatric micro- tubes (1 mm internal diameter and 2 mm length) and stored for either one or three months. (MSBS) was determined in a universal testing machine at a crosshead speed of 0.5mm/min. The results were analyzed with Mann-Whitney U and Kruskal-Wallis test. The significance level was set at P ≤ 0.05. Results: Significant differences in (MSBS) were found between enamel and dentin (P ≤ 0.05).Significant differences in (MSBS) were found between Etch&Rinse adhesive and Self-etch adhesive (P ≤ 0.05). (MSBS) of different storage period showed mixed results. Conclusion: Enamel remineralized with CPP-ACP acquired better bond strength when treated with etch and rinse adhesive system and The etch and rinse adhesive system had better performance in terms of bond durability to remineralized tooth substrates over time than the self-etch adhesive system.