Abstract: AIM: To observe whether hexarelin, a synthetic growth hormone-releasing peptide, protects rat thoracic aorta endothelial cells from H2O2-induced damage and to elucidate its mechanism. METHODS: Cultured endothelial cells from rat thoracic aorta were divided randomly into four groups: control group, H2O2 group, H2O2+10^-5 mmol/L hexarelin group and H2O2+10^-7 mmol/L hexarelin group. The morphology of endothelial cells was observed by contrast phase microscope and transmission electron microscope and cell viability was detected by MTT assay. Levels of lactate dehydrogenase (LDH) and nitrogen monoxidum (NO) were measured by supernatant. RESULTS: Contrast phase microscope and transmission electron microscope showed that H2O2 induced apoptosis of endothelial cells but hexarelin reversed the damage. H2O2 decreased endothelial cell viability (P<0.01), whereas 1×10-5 mmol/L/1×10-7 mmol/L hexarelin reversed the damage (P<0.01). H2O2 increased LDH release (P<0.01) but 1×10^-5 mmol/L/1×10^-7 mmol/L hexarelin decreased the LDH release (P<0.01). Compared with that in control group, H2O2 caused the reduction of NO (P<0.01), but 1×10^-5 mmol/L/1×10^-7 mmol/L hexarelin increased the NO. CONCLUSION: Hexarelin protects rat thoracic aorta endothelial cells from H2O2-induced damage and apoptosis, possibly through inhibiting the oxidative stress by increasing the NO levels.