Abstract: To clarify the mechanism of EDTA in the procession of ultrafine grinding of gypsum, viscosity, XRD, XPS and infrared spectroscopy were used to characterize the gypsum slurry and its ultrafine grinding products. The results showed that EDTA with a dosage of 0.40% could effectively strengthen the strain effect and grain refinement effect in the gypsum lattice and reduced the crystallinity and particle size of the gypsum, then reduced its d₅₀ from 42.43 μm to 16.69 μm under the conditions of a discharge port width of 12 mm, a slurry concentration of 20% and an ultra-fine grinding time of 15 minutes. Ca(COO)₂, generated by EDTA and Ca²⁺ of gypsum surface, covered hydroxylated active point Ca²⁺ which causes a negative increase in zeta potential, thereby reduced the relative content of adsorption water on the surface of the gypsum and the bonded force between the gypsum particles. The mentioned effects not only enhanced the repulsion between the gypsum particles to form a stable dispersion system, but also increased the turbidity of the gypsum slurry by 27.78% and decreased the viscosity by 18.16%, so improved the ultrafine grinding effect of EDTA on the gypsum finally.