SysGenSIM is a software package to simulate Systems Genetics (SG) experiments in model organisms, for the purpose of evaluating and comparing statistical and computational methods and their implementations for analyses of SG data [e.g. methods for expression quantitative trait loci (eQTL) mapping and network inference]. SysGenSIM allows the user to select a variety of network topologies, genetic and kinetic parameters to simulate SG data ( genotyping, gene expression and phenotyping) with large gene networks with thousands of nodes. The software is encoded in MATLAB, and a user-friendly graphical user interface is provided.