Isothermal compression tests were conducted at Thermecmaster-Z simulator, and grain size of the prior a phase was measured at a Leica LABOR-LUX12MFS/ST microscope for quantitative metallography. A methodology to establish a constitutive equation with grain size was proposed with the help of the experimental results. Combining FEM and the present constitutive equation at high temperature deformation, grain size of the prior a phase was simulated during the isothermal forging of a TC6 titanium alloy disc. The present results illustrate grain size and distribution of the prior a phase in the forging process of TC6 titanium alloy disc in detail. The maximum difference between the calculated results and the experimental is not more than 15%.