Transportation system facilitates the spread of pandemics across regions. This paper studies the modeling and optimal control of epidemic spreading with inter-city travel by train and bus. Considering the population spatial status, migration process, epidemic status and transport modes, a multi-regional migration-epidemic diffusion model is established by using dynamic equations. The diffusion properties are analyzed. With limited emergency resources, a dynamic optimal control model considering local and migration isolation strategies is also developed. Numerical examples compare the spread speed and scope of the epidemic under different control strategies, which verify the effectiveness of the proposed optimal control strategies. The results demonstrated that the epidemic could spread rapidly via the transportation system. Implementing a control strategy for certain type of transportation modes can quickly reduce the speed of cross-regional diffusion, but has little impact on the scope of diffusion.