The job-shop scheduling problem (JSP), which is one of the best-known machine scheduling problems, is among the hardest combinatorial optimization problems. In this paper, the key technology of building simulation model in Plant Simulation is researched and also the build-in genetic algorithm of optimizing module is used to optimize job-shop scheduling, which can assure the scientific decision. At last, an example is used to illustrate the optimization process of the Job-Shop scheduling problem with Plant Simulation genetic algorithm modules.