A detection support structure was designed to meet the need of a large-aperture off-axis rectangular mirror at an optical axis horizontal situation. Structure parameters were optimized to minimize the surface shape error caused by the detection support structure. Through comparing different cascaded multipoint lever support structures, a two-point support structure with simple structure, good extensibility and adjustment was chosen. Then,an integrated simulation and optimization method was used to analyze the trend curve of mirror surface shape changed with support interval and to obtain the optimized support interval. Finally, an interferometer combined with a compensator was used to measure the surface shapes corresponding to different support intervals and to verify the reliability of the simulation result. The result shows that the surface shape error caused by detection support structure reaches minimum at the support interval of 564 mm (RMS=8.26 nm), the trend curve obtained by simulation method agrees well with that obtained by the interferomety and shows a higher reliability. The method in this paper can be extended and applied to the design of detection support structure for other large aperture off-axis rectanglur mirrors, and can provide a foundation for off-axis Three Mirror Anastigmat (TMA) cameras.