Objective: To study nanostructural dentinal changes produced by endodontic irrigants. Study Design: Experimental study. Nanoindentations were performed on peritubular (PD) and intertubular dentine (ID) with an atomic force microscopy. Stiffness and adhesion force were determined before and after application of 5.25% sodium hypochlorite (NaOCl) and 17% ethylenediaminetetraacetic acid (EDTA). Normalized differences before and after treatment for stiffness and adhesion forces were calculated. A paired T-test was used to compare stiffnes and adhesion force before and after irrigants application. Results: After treatment with EDTA there was a 29.80% reduction in stiffness in ID and a 63.53% reduction in PD. Adhesion force was reduced by 21.22% and 8.21% respectively. After treatment with 5.25% NaOCI stiffness was reduced by 2.49% in ID and increased by 15.01% in PD. Adhesion force increased by 25.11% and 23.97% respectively. Conclusions: 17% EDTA reduced stiffness and adhesion force in ID and PD. Treatment with NaOCI at 5.25% had no significant effect on stiffness but did affect adhesion force in ID and PD.