Homocysteine (Hcy) and hypoxia can induce vascular endothelial dysfunction. The objective of this study was to compare the three models of rat vascular endothelial dysfunction which were established by Hcy, hypoxia and Hcy plus hypoxia, respectively. The assessment of models referred to vasoactive substances and neuro-endocrine-immunity network (NEI network). Fuzzy cluster analysis (FCA) and principal components analysis (PCA) were performed to process multivariate data from NEI network (containing 17 indices). The vascular endothelial function had all been impacted in the three models, while the levels of endothelin (ET) and von Willebrand factor (vWF) in hypoxia group had no significant differences when compared with the control. In the aspect of NEI network, the expression of neurotransmitter was disturbed in the Hcy group, while the systems of endocrine and immunity were out of balance in the hypoxia group, and the dysregulation of the whole NEI network was observed in the Hcy plus hypoxia group. The relationship between endothelial function and NEI network revealed that the levels of NO, vWF and soluble intercellular adhesion molecule-1 (sICAM-1) were associated with the expression of endocrine and immunity system, while the levels of ET and sICAM-1 were associated with the expression of neurotransmitters. The results indicated that some neurotransmitters may play a central role in Hcy induced endothelial dysfunction, while some markers of endocrine and immune systems may wide influence hypoxia induced endothelial dysfunction.