||The chemical genomics approach uses small molecules to modify or disrupt the function of specific proteins. It provides a novel avenue for rapid and effective dissection of biological mechanisms and gene networks in ways not feasible with mutation-based approaches. Vesicular trafficking is an essential cellular process driving the distribution of cargos within cells and maintaining subcellular structure. It basically underlies all cellular functions and can be modulated by both developmental and environmental signals. Despite the tremendous importance of this process, our knowledge on the underlying mechanism and the regulatory networks is very limited. In this study, we have developed a pollen-based high-throughput screen to select chemicals as inhibitors of pollen germination, a process absolutely dependent on intact vesicular trafficking. Using protein GFP-tagged, on a secondary screen, we are dissecting a network of genes controlling vesicle trafficking. By this approach, we expect to obtain novel regulators of the endomembrane system, which will be instrumental to further dissect mechanism of plant development.