Carotid intima-media thickness (IMT) and vascular inflammatory markers have been shown to be involved in atherosclerosis. This study was designed to investigate the effect of transdermal hormone replacement therapy (HRT) on carotid IMT and vascular inflammatory markers in postmenopausal women and to explore the interrelationship between the change in carotid IMT and the changes in vascular inflammatory markers. Thirty-five postmenopausal women (mean age 57.0+/-7.7 years) received transdermal HRT (continuous 17beta-estradiol patch [36 microg/day] plus cyclic oral medroxyprogesterone acetate [2.5 mg/day, for 12 days/ month]) for 12 months, and 32 controls (mean age 58.0+/-7.5 years) did not. Carotid IMT, assessed by ultrasound, and circulating vascular inflammatory markers, i.e., C-reactive protein (CRP), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, E-selectin, monocyte chemoattractant protein (MCP)-1, and matrix metalloproteinase (MMP)-9 were measured before and after 12 months of treatment. In the HRT group, carotid IMT decreased significantly (p<0.01), from 0.71+/-0.13 mm to 0.65+/-0.12 mm, and the ICAM-1, VCAM-1, E-selectin, and MCP-1 levels decreased significantly (p<0.01 for all), but the CRP and MMP-9 levels remained unchanged. Carotid IMT and vascular inflammatory markers were unchanged in the control group. In the HRT group, the change in carotid IMT was significantly correlated with the change in serum E-selectin (r=0.38, p<0.05), but not with the changes in other vascular inflammatory markers. These results suggest that transdermal HRT reduced carotid artery wall thickness, and that the reduction may have been induced by an antiatherosclerotic effect combined with the direct effect of estrogen and decreased levels of estrogen-induced E-selectin.