Introduction: The aim of the present study was to evaluate the effect of magnesium oxide as an irrigant prepared from nano or microparticle sizes on extracellular PH changes around human dental pulp stem cells. Methods: To evaluate PH changes around dental pulp stem cells, a composite of the cells with different irrigation solutions were prepared and classified into six groups: Group I, 1.5 % sodium hypochlorite solution. Group II, 17% EDTA solution. Group III, 1.5 % sodium hypochlorite solution and 17% EDTA. Group IV, 5mg/L magnesium oxide (microparticles) solution. Group V,5mg/L magnesium oxide (nanoparticles) solution. Group VI was the negative control group without any treatment. The cell cytotoxicity assay was performed using Methyl Thiazol Tetrazolium (MTT) Assay after 1 hour, 24 hours and 72 hours of incubation with the tested irrigants. In addition, Assessment of pH of hDPSCs treated with various solutions was performed. Data were statistically analyzed. Results: With time, pH of cells' culture decrease, and the percentage of cell's viability increase for all tested solutions. Conclusions: The increase of % viability for hDPSCs cultured with different irrigation solutions is accompanied by decrease of the extracellular pH around the cells.