Based on the TRIP 3.0 (TRIsonic Platform V3.0) software and structure grid technology, the effects of different mesh topologies and control equations on aerodynamic characters of DLR-F6 wing-body configuration are studied. The study is implemented with the RANS/TLNS equations, as the same parameters of the experiment are used. Coarse, medium and fine meshes of O and H topologies are also generated for the simulation. The effects on the simulation of DLR-F6 wing-body configuration are studied from aerodynamic characters, pressure coefficient distribution curve and flow pattern on the surface. Compared with experimental data, the numerical results indicate that more accurate results can be obtained by adopting the H topology mesh and RANS equations on the simulations of flow field with small separation zone. © 2017, Press of Chinese Journal of Aeronautics. All right reserved.