During atherosclerosis process, vasoconstriction phenomenon occurs which in turn leads to tissue hypoxia. A few studies have been performed on the combination of atherosclerosis and hypoxia as stressors that may accelerate secretion of constrictors. The aim of present study was to evaluate the effects of atherosclerosis and hypoxia on serum levels of main vasoconstrictors (epinephrine, norepinephrine and renin). In this interventional study, 32 New Zealand white rabbits were randomly divided into four groups (n = 8): normal diet (control group), normal diet exposed to hypoxia (11%, 10 days), high-fat diet (cholesterol-2%, 8 weeks), and high-fat diet with hypoxia. Later, serum levels of renin, epinephrine and norepinephrine were measured on second, 56th and 66th days. High-fat diet and hypoxia caused significant increase in epinephrine and norepinephrine concentrations on days 56 and 66 compared to the control group (P < 0.05). Also, renin showed significance increase in high-fat diet and high-fat diet+ hypoxia groups compared to the control group (P < 0.05). Both high-fat diet and hypoxia increase renin levels in male rabbits. Furthermore, the combination of high-fat diet and hypoxia immensely increases renin levels. Both hypoxia and combined of high-fat diet and hypoxia increase norepinephrine levels. However epinephrine is only increased in the combination of high-fat diet and hypoxia. So the presence of hypoxia in combination with high-fat diet, cause accelerated and aggravated atherosclerosis.