Aim To explore whether the autocrine and paracrine secretion of the damaged endothelial cells (EC) can regulate the damaged EC and the effect of hypothalamus-pituitary neuroendocrine axis on the autocrine and paracrine secretion of the damaged EC. The changes in the metabolism of lipid peroxide (LPO) and the expression of inducible nitric oxide synthase (iNOS) were detected through the influence of conditioned media of endothelial cells (EC-CM) induced by diamide and affected by hypothalamus-pituitary cells on injured EC respectively. Methods The normal EC-CM was used in the control group. In the experimental group, the EC-CM induced by diamide and the EC-CM induced by both conditioned medium of hypothalamus-pituitary cells and diamide were prepared. The EC injured by diamide were cultured respectively with the above three EC-CM. After culturing with the three EC-CM, all EC of the experimental and control groups were cultured in serum-free medium. Then the supernatant of the above serum-free media and cultured EC were collected for detecting the content of LPO and iNOS. Results It was shown the EC-CM induced by diamide and the EC-CM induced by both conditioned medium of hypothalamus-pituitary cells and diamide had down regulative effect on the metabolism of LPO and up regulative effect on iNOS expression of injured EC. However, the medium containing hypothalamus-pituitary tissue showed more intensive anti-lipid peroxidation effect. Conclusion It is suggested that when EC was damaged by diamide, its autocrine and paracrine secretion can regulate its LPO metabolism down and regulate its iNOS expression up, which might be one of the mechanisms in EC for defending against external injury.