With embedded system being used in every corner of military and civil electronic industries, its security problem is prominent. Inspired by the natural immune system, the paper proposes an immune middleware to prevent embedded system from misacting when net intrusion or inner mistake happens. Firstly a flexible bus that has three-layer architecture is presented to help the embedded system acquire compatibility, multifunctionality and standardization. Then based on this multiplayer bus architecture, the middleware evolved from the concept of antigen and antibody is proposed. The design principle, the immune strategy, the architecture and the working flow of the immune middleware are introduced in detail afterwards. Finally an experimental case demonstrates the validity of the proposed method.