Purpose: Inflammation plays a major role in all phases of atherosclerosis. Homocysteine and fibrinogen is two inflammatory markers predictor of atherosclerosis risk. The purpose of this study was to investigate the effect of regular aerobic exercise and consumption of omega-3 supplementation on serum Homocysteine levels and fibrinogen in obese elderly women. Method: In a double-blind study, 40 obese women (BMI≥30) 61.65+7.42 years old were selected as easily-accessible way and randomly categorized into 4 groups of 10 subjects an exercise, supplementation, exercise-supplementation (combination), and placebo (control) groups. Subjects in the supplement and combination groups consumed 2080 mg omega- 3 supplement daily for 8 weeks and control groups used sunflower oil as placebo produced in Zachariah Company. Exercise program included aerobic activity at 45 to 55 percent of maximum heart rate for 8 weeks, 40 minute and 3 sessions per week. Blood samples before and 24 hours after the training period in the fasting state were collected. Data analysis was done by paired-t test and two-way ANOVA test using SPSS software (version 16). Result: The results showed that interaction effects of exercise and supplementation has co-increment impact on significant reduction of Homocysteine and fibrinogen means (P<0.05). Conclusion: The results of this study showed that acrobic training combined with omega-3 supplements can by reducing body fat percent and restrict of upstream inflammation signals decreased cardiovascular risk factors and minimize the negative effects of inflammation in obese elderly women.