The impacts of slag composition on the CaO content in inclusions during vacuum degassing(VD) treatment are presented. Industrial trials and thermodynamic calculations are used to test, analyze and identify proper optimization method. After optimization, the CaO content of inclusions after VD treatment decreases from 11.3mass% to 7.4mass%. Furthermore, the quantity of CaO containing inclusions in hot-rolled bar decreases from 146 to 41 as well. It is found that the ideal kinetic conditions and the evaporation of Ca during VD process combined trigger and are expected to further enhance the reaction between Al in liquid steel and CaO in slag. Some of the Ca generated from slag will further react with the inclusions which leads to the increase of CaO content in inclusions and equivalent circle diameter of the inclusions. The mathematical correlations among the components of slag in equilibrium with that of liquid steel is obtained by thermodynamic calculations.