The microcirculatory vascular tone and the regional blood flow are regulated by an elaborate network of intracellular and extracellular signaling pathways with multiple feedback control loops. This complicates interpretation of experimental data and limits our ability to design appropriate interventions. Mathematical modeling offers a systematic approach for system and data analysis and for guiding new experimentation. We describe here our efforts to model signal transduction events involved in the regulation of blood flow and integrate mechanisms at the cellular level to describe function at the multicellular/whole-vessel level. The model provides a) a working database of rat mesenteric endothelial and smooth muscle physiology where newly acquired experimental information on cell electrophysiology and signal transduction can be incorporated, and b) a tool that will assist investigations on the regulation of vascular resistance in health and disease. An example of model application to the study of the pathogenesis of salt-sensitive hypertension is illustrated.