Abstract : This in vivo study aimed to investigate the effect of matrix metalloproteinase MMPs inhibitors (2%chlorhexidine digluconate (CHX), and ethylene diaminetetra acetic acid (EDTA) on microtensile bond strength to dentin using etch and rise adhesive. Nine adult mongrel dogs of age range (12 -18 months) were included in the study. A total of 90 standardized class I cavity were prepared in upper and lower (canine - first and second molar). The teeth were divided into three main groups (n = 30) according to the type of MMP inhibitors were used: the control group (no MMPs inhibitors were applied), the CHX group, and the EDTA group. Each group were divided into three subgroups (n=15) according to the testing periods 6 and 12 months. At the end of each testing period, animals were sacrificed, teeth were separated from the jaws, mounted on cutting machine, and sectioned into a series of 1mm thick slabs. Micro-tensile bond strength was measured for each sample by using universal testing machine. Data were tabulated and statistically analyzed. Results of micro-tensile bond strength showed that after 6 months, there was a significant difference between MMPs inhibitors, while after 12 months the difference was not statistically significant. The control and CHX groups showed a significant higher values than EDTA. This study concluded that MMP inhibitors did not interfere with micro-tensile bond strength of composite to dentin, with slightly significantly increased in CHX. Micro-tensile bond strength decreased by aging time and the best results were in 6 months of aging periods.