Objective To assess the effects of hormone replacement therapy (HRT) on platelet activation in postmenopausal women compared with premenopausal women. Methods The expressions of 0D41 and CD62P in fifteen postmenopausal women before and after HRT were detected using flow cytometry (FCM), with fifteen premenopausal women with a mean age of 47 years as controls. Results The expressions of 0D41 and CD62P in postmenopausal women were higher than those in the control group. CD62P(%), CD62P(I) and 0D41 were reduced from 36.40±5.9, 37.75±5.8, and 470.11±74.0 to 27.97±5.6, 26.64±4.9, and 303.23±72.8 after six months of HRT (P＜0.05). Conclusions Platelet activation in postmenopausal women was higher than in premenopausal women and was reduced significantly after six months of HRT. HRT may have a favorable effect on reduction of platelet activity.