One of the most important issues in the flight control system of a space plane is how to overcome various uncertainties. This study aims to design a nonlinear adaptive flight control system based on the Immersion and Invariance (I&I) method to tolerate the uncertainties of parameters. In general, it is difficult to acquire several exact parameters, such as stability derivatives, of a space plane because of its wide flight envelope. Therefore, it is necessary to design a nonlinear fight control system under the condition where uncertainties of parameters exist. This study focuses on the I&I which is a new adaptive control method. In this study, the unknown parameters are considered to be multiplicative uncertainties toward the rigorous dynamics model because the controller designed by this kind of method can tolerate not only the specific disturbance but also various uncertainties. The flight control system based on the I&I is applied to space plane model and the availability of the proposed flight control system is verified by the six-degree-of-freedom nonlinear simulation.