This paper presents the scheduling of Flexible Manufacturing System (FMS) using discrete event simulation. Simulation models have been developed using Arena, for three basic FMS layouts and four scheduling rules: First-Come-First-Serve (FCFS), Shortest Processing Time (SPT), Longest Processing Time (LPT) and Earliest Due Date (EDD). Automatic Guided Vehicles (AGVs) are used as the Material Handling System (MTH) in the system. The scheduling rules in each of the individual FMS layouts are evaluated and compared in relation to five output measures: number of products being produced, average machine utilization, mean flow times, mean queues and mean tardiness. The simulation results are analyzed and discussed in detail and conclusions have been drawn on scheduling rules that yield best results in given scenarios, with the SPT rule performing the best (LPT being the worst). The more important result shows that the effect of the scheduling rules have much greater impact on the output performance measures than the differing FMS layouts.