Background: Globally, the prevalence of overweight and obesity is increasing, predisposing both sexes to health hazards including cardiovascular diseases and death. Objective: Evaluation of the effects of flaxseed oil on vascular health in hyperlipidemia. Material and methods: Forty adult male albino rats of local strain between 7-8 weeks-old weighing 130-150 g were used. The rats were divided into four equal groups: Group I (control group), Group II (hyperlipidemic group), Group III (HFD-flaxseed oil prophylactic-group), Group IV (HFD-flaxseed oil treated-group). At the end of the experiment body weight, as well as serum levels of lipid profile, malondialdehyde (MDA), reduced glutathion (GSH), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and vascular cell adhesion molecule 1 (VCAM1) were determined for all groups. Results: Flaxseed oils pretreatment and treatment significantly decreased body weight. Serum cholesterol, triglycerides and LDL significantly decreased, while HDL significantly increased. Furthermore, flaxseed oil suppressed the increase in MDA, serum IL-6, TNF-α, and VCAM1 level and elevated the serum GSH level significantly. Conclusion: Flaxseed oil possessed anti-atherogenic actions that might be mediated by their reducing effect on the lipid profile and inflammatory markers. Pretreatment was more effective than its use as a treatment. Thus, flaxseed oil may have the therapeutic potential in atherosclerotic patient and may be a novel therapeutic strategy for atherosclerosis prevention and treatment.