INTRODUCTION: Rheumatoid arthritis (RA) is the most common systemic autoimmune disease resulting in excessive cardiovascular complication and mortality secondary to endothelial dysfunction. Recently many clinical trials have been carried on the role of omega-3 fatty acid supplementation in regression of symptoms of diseases. The exact mechanisms underlying such association are still not fully elucidated. AIM OF THE WORK: To evaluate the effect of omega-3 on endothelial dysfunction as well as assess the level of vascular cell adhesion molecule (VCAM) and malonaldehyde (MDA) in rats with adjuvant arthritis. MATERIALS AND METHODS: After approval of the Ethics Committee of Faculty of Medicine, Alexandria University, 30 male albino rats (125-150 grams) were used in this study. Rats were kept under standard laboratory conditions. The rats were divided into 3 groups 10 rats each. Group I: control group, Group II: RA induced group and Group III: RA induced group + omega3 supplementation. Induction of RA in 20 rats was done by intradermal injection at base of tail (120 μL of 1 mg of heat-killed Mycobacterium butyricum suspended in 0.1 ml of mineral oil). Induction of RA was confirmed by clinical sign of arthritis on day 11 of induction. The study duration was 30 days from the day of induction. In group III Omega 3 was given orally once daily by an intra-gastric tube, at a dose of 300 mg/kg (equivalent to 0.02 ml fish oil/rat, the omega-3 started on the day 11 after the induction of RA (appearance of clinical arthritis) continued to end of the study. At the end of study, clinical scoring of arthritis was repeated. Then all rats anaesthetized by ether inhalation to be sacrificed by decapitation, blood samples were collected for VACM and MDA assessment in serum and section of Aorta was taken to test vascular reactivity to acetylcholine and noradrenaline using power lab AD instrument. RESULTS: Values are expressed as means ± SD, compared by ANOVA. Both VCAM and MDA were increased significantly after RA induction in group II ( 10 ±1.3 ng/ ml & 8.9 ± 1.6 nmom/ml respectively) in comparison to group I ( 5 ±0.45 ng/ ml & 3.5 ± 0.7 nmom/ml respectively) with p<0.05 for both of them. Treatment with omega-3 significantly decreased VCAM (7.2 ±1.42 ng/ ml) & MDA (5.2 ± 1.2 nmom/ml) in group III in comparison to group II with p<0.05 for both of them. Plasma VCAM is negatively correlated with Ach-induce relaxation of thoracic Aorta. (r = -0.723 and P = 0.000) CONCLUSION: The present study highlights the importance of omega-3 in RA to slow down the progression of endothelial dysfunction by its effect on vascular reactivity and oxidative stress. The decreased VCAM levels seen with omega-3 may contribute to this improvement.