Abstract INTRODUCTION: The objective of this study was to evaluate the effect of L-arginine (L-Arg) and L-NAME on coronary vascular and aortic endothelial permeability in normocholesterolemic (NC) and hypercholesterolemic (HC) rats. METHODS: Forty-eight male rats were divided into NC and HC groups and each group was divided into L-Arginine-treated, L-NAME-treated and control subgroups. L-Arg (2.25%) and L-NAME (0.75 mg/ml) were dissolved in drinking water and control groups received tap water. After 8 weeks, endothelial permeability was assessed by using the Evans Blue (EB) dye method. RESULTS: Aortic endothelial permeability was significantly higher in HC group compared to NC group (15.1±0.7 vs. 7.7±0.8 µgEB/g tissue, respectively; P<0.05). L-Arg and L-NAME treatment decreased aortic endothelial permeability in HC animals (L-Arg: 8.4±0.4 & L-NAME: 10.8±0.6 vs. 15.1±0.7 µgEB/g tissue, respectively; P<0.05). There was no significant difference in endothelial permeability in coronary circulation between HC and NC groups and L-Arg and L-NAME did not alter endothelial permeability. CONCLUSION: It seems that L-Arg and L-NAME have different effects on endothelial permeability based on physiological and pathological conditions and type of vessel. Keywords: L-Arginine, L-NAME, nitric oxide, endothelium, permeability.