To investigate the lithospheric structure and deformation of the Tibetan Plateau, we present thermo-rheological models for two transects across the southeastern Tibetan Plateau (SE Tibet), showing strong lateral heterogeneity. The geodynamic implications are also investigated in relation to GPS motions, seismic anisotropy, seismicity distribution and crustal isostatic state. The unmatched pattern between Pms and SKS splittings which even intersect at right angles to the south of 26°N, suggests the crust-mantle decoupling. Constrained by a brittle load-bearing layer at the uppermost mantle beneath the Indochina block, the decoupling may occur below the uppermost mantle. The strong crust beneath the South China plate and Indochina block implied by the seismicity distribution, has two thick brittle load-bearing layers, indicating a coupled system. The crust beneath the Emeishan large igneous province (ELIP) also has two brittle load-bearing layers, but the brittle deformation is restricted to the topmost 10 km of the upper and lower crust. Only one brittle load-bearing layer resides in the upper crust in the other part of the Chuandian block. Combining with GPS and Pms splitting, we can infer that the weak crust with seismicity restricted into the depth of <30 km beneath the Chuandian block becomes decoupled. The heterogeneous rheological behavior under SE Tibet is further supported by different crustal isostatic states among the blocks. Through the comparison with observations in the central-northern Tibetan Plateau and Chuandian block, we suggest that the layers with aqueous fluids and (or) partial melting are distributed only in some place/channels of the weak middle-lower crust.