Abstract: For the realization of the standardized, scientific, accurate and rapid emergency rescue process, this paper conducted a research based on multi-agent rescue technology for the major accident rescue after disasters of high-speed railway. The paper introduced the multi-agent theory and technology to the high-speed railway major accident rescue field after disasters, built a disaster space simulation model for high-speed railway operation process major accident rescue, dissected the cooperation rescue model between similar multi-agents and heterogeneous multi-agents in the high-speed railway emergency rescue process, analyzed the accident cases rescue after a high-speed railway station of emergent disaster and a high-speed railway line post-disaster relief, proposed specific suggestions, further demonstrated the efficiency and scientificity of the simulation of high- speed railway rescue. Research results show that the high-speed railway multiple agent rescue simulation can reproduce the progress of the rescue and predict the direction of disaster development, provide reference for the optimization of rescue mission strategy after the actual disaster, display detailly the disaster spread, the rescue process, and so on in real time, provide a direction for the future development of the smart high-speed railway rescue field.