The earliest step in the development of atherosclerosis (AS) is the recruitment of leukocytes to vascular tissues. Vascular cell adhesion molecules 1 (VCAM) may play a central role in promoting the adhesion of the leukocytes to the endothelium. Regular exercise (EX) reduces the incidence of AS and the underlying mechanisms of this protective effect remain to be investigated. The relationship between regular EX and VCAM-1 has not been well studied. We investigated the relationship between regular EX and soluble VCAM (sVCAM) in seventeen healthy volunteers (M:F = 5:12, age = 39.3 ± 15.2 yrs, mean ± SD). The amount of time spent in EX was obtained by questionnaire and the mean levels were 24.2 ± 23.9 min/day. Plasma sVCAM was measured by ELISA kit and the mean levels were 524 ± 135 ng/mL. An inverse relationship was found between sVCAM and regular EX (sVCAM = -3.14 *EX + 600, r = -.5543, p = .021). sVCAM tended to be associated with BMI (r = .373, p = .14) and plasma cyanocobalamin levels (r = .353, p = .16). The relationship between EX and sVCAM remains significant when adjusted by age, sex, race, BMI, and plasma levels of cholesterol, triglyceride, and cyanocobalamin (p = .0283, R2 = .81). Our findings in human subjects are in agreement with animal studies that indicate chronic exercise decreases the expression of VCAM in aorta tissues and suggest that a decreased VCAM expression due to regular EX can be a mechanism for the protection of AS by EX.