Vascular endothelial cells (EC) and smooth muscle cells (SMC) are target and effecter cells of inflammation, and they play an important role in inflammatory responses. The abnormal structure and function of EC and SMC play a significant role in microcirculation disturbance in septic shock and multiple organ dysfunction. This review was meant to discuss the changes in structure and function of EC and SMC and their bidirectional regulation. The cellular linkage of EC and SMC is essential for the interactions between them, and it contributes to the course of sepsis. Paracrine and autocrine as produced by EC and SMC constitute a network for mutual adjustment. Replication of the interaction between EC and SMC facilitates the potential to support hemodynamics, tissue perfusion and cellular metabolism, thereby lower the mortality rate of sepsis. However, the detailed and specific mechanisms remain to be disclosed.