Biomaterials have become the critical component in the development of small diameter vascular graft. In this project, the suitability of a biomaterial, rich in collagen and other growth factors, derived from the porcine small intestine submucosa (SIS) to be used as a small diameter vascular substitute was studied. Endothelial cells (ECs) are the innermost cell linings of the lumen of all blood vessels. The morphology of ECs cultured on SIS was examined in vitro using scanning electron microscopy. Results showed that endothelial cells became round shape, proliferated and attached to the surface of SIS to form a confluent monolayer. Organization of the cytoskeleton of the endothelial cells cultured on SIS and on glass slides coated with Type I collagen was also examined using fluorescent immunostaining. Actin bundles were relatively thin and disorganized in endothelial cells seeded on SIS. Thick actin filaments were found at the periphery of the cells seeded on glass slides coated with Type I collagen. This different organization could be due to the porosity, composition and hydrophilicity of the biomaterials used. During cell inflammation, monocytes were found adhering to ECs in the blood vessels causing ECs dysfunction. Activated leukocytes and macrophages release proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) to enable ECs to increase their expression of adhesion molecules. In addition, TNF-a also causes ECs to produce vasodilators to increase blood flow to the affected area. Monocytes adhesion to endothelial cells was most likely the consequences of inflammation that might lead to the graft rejection. Human monocytes THP-1 cells were used to study the adhesion assay of monocytes to ECs seeded on SIS and glass slides coated with Type I collagen using fluorescent microscope. When activated with TNF-α, THP-1 cells showed more prominent adhesion to ECs cultured on glass slides coated with Type I collagen as compared to SIS. This result suggested that TNF-α induced higher number of endothelial cells-monocytes interaction on glass slides coated with Type I collagen compared to SIS.