In this article, the microstructure evolution and mechanical property of Ti-22Al-25Nb（at. %） alloy after different phase region isothermally forging and heat treatment were studied. The results indicated that as the isothermally forging temperature increased from 980℃（α2＋O＋B2 three phase region) to 1060℃（B2 phase region), the microstructures of alloys showed that equiaxed microstructures, duplex microstructures, and bimodal size lamellar O microstructures. The size and volume fraction of each phases couble be controlled by heat-treatment schedule. The mechanical properties of alloys showed that bimodal size lamellar O microstructures have the biggest strength but the poor ductility; however, equiaxed microstructures have the biggest ductility but the poor strength. The equiaxed microstructures have the worst creep resistance, the duplex microstructures and the bimodal size lamellar O microstructures have similar creep resistance.