Abstract: Vascular Endothelial Growth Factor (VEGF) and Nitric Oxide (NO) play an important role for maintaining endothelial integrity. The purpose is to investigate the VEGF alteration during early atherosclerosis lesion formation in an animal model of hypercholesterolemia. We also measured nitrite to observe the relationship between VEGF and endothelial NO production. 20 white male rabbits randomly assigned in 2 groups (1% high-cholesterol diet, HC group, n = 14, or standard diet, control, n = 6) for 4 weeks. The serum levels of VEGF and nitrite (NO metabolite) were determined. Fatty streaks were measured in rabbit’s aortas. The results indicated that the serum level of VEGF concentration was significantly higher in hypercholesterolemic rabbits and negatively correlated with fatty streak lesions (r = -0.89, p<0.05). The serum level of nitrite was significantly higher in HC group than the control (p<0.05). There was a significant negative correlation between serum level of nitrite and VEGF (r = -0.55, p<0.05). It is concluded that, the increased VEGF in early atherosclerosis may be regarded as a safeguarding response to endothelial injury, which is responsible for maintaining endothelial integrity.