Cardiovascular diseases such as atherosclerosis are considered as the main causes of mortality in today’s industrial world. Increase of the basal level of high sensitive C-reactive protein (hs-CRP) and Homocysteine have been introduced as the main and independent next major risk factors for cardiovascular disease. The purpose of this study was to investigate the effect of a single circuit-resistance on blood levels of these inflammatory markers in overweight women. Twenty one subjects were randomly assigned into experimental and control group. The exercise program included nine stations whit 40% one-repetition maximum subjects. Blood levels of hs-CRP and Homocysteine were measured before and immediately after exercises. Dependent t and independent t were used in the two groups and between the groups respectively to compare pre-test and post-test data. The findings indicated that, the levels of hs-CRP and Homocysteine after exercise had a significant increase compared to before the exercise (P<0.05). The variations were also significant compared to the control group, hs-CRP and Homocysteine respectively )P=0.003, P=0.001). The results of correlation coefficient in the present study showed no significant statistical relationship between hs-CRP and Homocysteine )P=0.587, r=0.175). A single circuit-resistance exercise with 40% of 1RM causes to increase of the levels of hs-CRP and Homocysteine in overweight women. Considering the different achieved results in different studies, more researches are needed on the impact of acute physical activities as well as long-term periods on the levels of risk factors for atherosclerosis.