Vacuum induction melting device combined with temperature control system was employed to investigate the effect of isothermal heat treatment (IHT) during solidification process on the microstructure evolution of a high Nb containing TiAl alloy. The microstructures of the alloy in as-cast condition and after IHT were studied. The results show that the as-cast microstructures exhibit a significant microstructural inhomogeneity with fine grains in dendrite core and coarse grains in interdendritic region. A new treatment approach by means of a short-term IHT within the β phase field during solidification process is proposed to obtain a uniform and refined microstructure. Compared with the as-cast alloy, IHT can reduce the tendency for crack. This phenomenon is attributed to the improvement of microstructural homogeneity by the elimination of peritectic α phase and the microstructure refinement by β → α transformation.