Background: Obesity, a sort of dietary imbalance, is one of the most frequently encountered medical problems associated with many complications as hypertension, hyperlipidemia, and seems to make morphological alterations of kidney too. Pumpkin seeds oil (PSO) is rich in unsaturated fatty acids, antioxidants and fibers. Objective: Evaluation of the efficiency of using PSO on regulation of arterial blood pressure, cardiac and renal health in high fat diet (HFD)-treatedrats. Materials and methods: Thirty adult male albino rats were divided into three equal groups: Group I (control group), Group II (HFD-treated group), Group III (HFD & PSO 100 mg/kg-treated group). At the end of the experiment body weight, mean arterial blood pressure (MABP) and electrocardiogram (ECG) were determined for all groups. These were beside measuring serum levels of lipid profile (TC, TG, LDL and HDL), urea, creatinine, nitric oxide (NO), malondialdehyde (MDA), reduced glutathion (GSH), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and vascular cell adhesion molecule 1 (VCAM1). The effect of different doses of PSO (75-1200 μg/ml) on norepinephrin-induced contractionsof isolated rabbit aortic spiral strips was recorded also. Kidney samples were taken and processed for light and electron microscopic examination too.  Results: PSO significantly decreased body weight, blood pressure, heart rate and kidney function tests in HFD rats. Serum cholesterol, triglycerides and LDL significantly decreased, while HDL significantly increased. Furthermore, PSO suppressed the increase in MDA, IL-6, TNF-α and VCAM1 levels and elevated GSH level significantly. Histological examination revealed that PSO improved the kidney structure as it decreased the extent of renal tissue damage and interstitial fibrosis in HFD rats. Also it decreased the norepinephrin-induced contraction in aortic strip of rabbit. Conclusion: PSO possessed anti-atherogenic action by its ameliorative effect on the lipid profile, kidney functions, inflammatory markers, kidney structures and its effect on aortic strip. Thus, Pumpkin may be a novel strategy for prevention and treatment of atherosclerosis and hypertension.