Aim To investigate whether hypothalamus-pituitary neuroendocrine pathway influenced the development of atherosclerosis. Methods The hypothalamic and pituitary tissue from freshly aborted 5-month human fetuses were taken for cellular culture and the condition media were collected respectively according to hypothalamus, pituitary and hypothalamus+pituitary groups. The normal endothelial cells and those induced by diamide were cultured respectively with the condition media and the control group with ordinary medium. After culturing with the condition media, all endothelial cells of the experimental and control groups were cultured in serum-free medium. Then collected the serum-free media of the EC separately and detected their content of lipid peroxide and nitric oxide. Results The pure hypothalamus or pituitary group had intensive effect of lipid peroxidation on endothelial cells and did not affect the release of nitric oxide from endothelial cells when the pure hypothalamus or pituitary conditioned media were used. The content of lipid peroxide in hypothalamus +pituitary group was significantly lower than that in other experimental groups (hypothalamus group and pituitary group), but the nitric oxide showed an inhibited function. However, the hypothalamus+pituitary group performed an anti-lipid peroxidation function to the endothelial cells induced by diamide and an increased releasing of nitric oxide. Conclusion From the result we deduced that the hypothalamus may play a significant role in keeping normal function of the endothelial cells, and the effect may be through the hypothalamus-pituitary pathway. When meeting with the harmful factors it can play a protective role in maintaining the function of endothelium.