The opioid peptides modulate extensive bioactivities, including pain, cardiovascular response, development and further responses. In the present study, the stimulative effects of endogenous opioid peptides on angiogenesis are evaluated in the proliferation, migration, adhesion and tube formation assays of the human umbilical vein endothelial cell (HUVEC) for the first time. Endomorphin-1, endomorphin-2 and deltorphin I at physiological concentrations could stimulate HUVECs proliferation, migration, adhesion and tube formation in a dose dependent manner; whereas, they exhibited the cytotoxic effects on HUVECs at the higher doses in these assays. Naloxone, the nonselective opioid receptor antagonist, did not influence angiogenesis when it was administrated on its own; but it could antagonize the stimulative effects of the opioid peptides on angiogenesis when it was administrated in combination with the opioid peptides. Taken altogether, the results suggested that endogenous opioid peptides (endomorphin-1 and -2 and deltorphin I) stimulated angiogenesis at the cellular level, and these effects were mediated by the opioid receptors. These data are significant for potential clinical implementation in future.