With the improvement of requirements in resolution and system′s viewing about aerospace remote camera, off-axis four mirrors optical system has attracted more and more attention. Traditional design method in the off-axis system is gradually reaching its limitations. Therefore, a new design method based on differential equations is presented. Firstly, it introduces the principle and design idea of this design method by differential equations, and the restriction factor of the focal length, then an innovative coaxial four mirrors model is put forward. Finally, according to the differential equations method, a large field of view off-axis four mirrors optical system is designed, in which focal length is 100 mm, the field angle in sagittal direction is 40°, the field angle in meridian direction is 10°, the modulation transfer function (MTF) is above 0.606 at the 50 lp/mm. By experimental verification, the design method of differential equations is not only simple and effective in computation, but which also has a wide application prospect in the calculation of structure parameters of off-axis system and surface calculation.