Recently, it was shown that substituting soy nuts for nonsoy protein in a therapeutic lifestyle change (TLC) diet lowered systolic and diastolic blood pressure by 9.9% and 6.8%, respectively, in postmenopausal women with hypertension and by 5.2% and 2.9%, respectively, in normotensive postmenopausal women. In this study, to examine mechanisms for these reductions, markers of inflammation were measured, including soluble vascular cell adhesion molecule–1, soluble intercellular adhesion molecule–1, C-reactive protein, interleukin-6, and matrix metalloproteinase–9. Sixty healthy postmenopausal women (48 normotensive and 12 with hypertension) were randomized in a crossover design to a TLC diet alone or a TLC diet in which 0.5 cups of soy nuts (25 g soy protein and 101 mg aglycone isoflavones) replaced 25 g of nonsoy protein daily. Each diet was followed for 8 weeks. Compared with the TLC diet alone, levels of soluble vascular cell adhesion molecule–1 were significantly lower on the soy diet in women with hypertension (623.6 ± 153.8 vs 553.8 ± 114.4 ng/ml, respectively, p = 0.003), whereas no significant differences were observed in normotensive women. Soy nuts were associated with a trend toward reduction in C-reactive protein in normotensive women. No effect on levels of soluble intercellular adhesion molecule–1, interleukin-6, or matrix metalloproteinase–9 was observed. In conclusion, the reduction in soluble vascular cell adhesion molecule–1 with soy nuts in women with hypertension suggests an improvement in endothelial function that may reflect an overall improvement in the underlying inflammatory process underlying atherosclerosis.