The purpose of this paper is to explain aerodynamic interaction effects from upstream and downstream on the down-flow type exhaust diffuser performance in a low pressure steam turbine. To increase exhaust diffuser performance, design data related to the aerodynamic interaction effects from upstream turbine stages and downstream exhaust hood geometry on the exhaust diffuser performance would be very useful. This paper presents numerical investigation of three dimensional wet steam flows in a down-flow type exhaust diffuser with non-uniform inlet flow from a typical last stage with long transonic blades designed with recent aerodynamic and mechanical design technology. Previous studies show that small scale model tests and CFD analyses of exhaust diffusers with uniform inlet flow conditions are not enough to investigate diffuser efficiency and detail diffuser flow mechanism because inlet flow structures including tip leakage flows and blade wakes superimposed from a last stage and several other upstream turbine stages in low pressure turbines affect flow separations that reduce the exhaust diffuser performance. Recent studies by the authors show that the introduction of radial distributions of velocities and flow angles at the inlet section of exhaust diffuser measured in a full scale development steam turbine increased the accuracy of numerical analysis of diffuser flow. In the present study, the computational domain was enhanced and the method of boundary condition definition was improved to increase the accuracy of boundary layer separation and separation vortex generation in wet steam flows. Using the improved method, the calculation results explained the aerodynamic interaction effects from upstream and downstream on the down-flow type exhaust diffuser performance.