Epidemiologic studies have revealed a higher incidence of cataracts in estrogen-deprived postmenopausal women, although the pathogenic mechanism has not yet been elucidated. Apoptosis of lens epithelial cells has been associated with cataractogenesis. The aim of the study reported here was to investigate the effect of estrogen replacement therapy (ERT) on lens epithelial cell apoptosis in an experimental rat model. Forty female Wistar rats were randomized into four groups: ERT (17beta-estradiol, 10 microg/kg/day) for 3 months without ovariectomy (group 1) and with ovariectomy (group 2); only ovariectomy (group 3); sham operated (group 4). At the end of the third month, all rats were sacrificed in estrous cycle, as determined by the vaginal smear test, and their right eyes were enucleated. Enucleated eyes were analyzed by immunohistochemical methods for the expression of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end (TUNEL), caspase-3, and bcl-2 labeling. The TUNEL, caspase-3, and bcl-2 staining scores were found to increase in group 3 rats following the ovariectomy compared to the sham-operated group. The ERT decreased these scores in rats with or without the ovariectomy; however, these differences were not statistically significant. These data suggest that estrogen does not significantly affect lens epithelial cell apoptosis. Further studies are needed to gain a better understanding of the protective mechanism of estrogen and to provide new ideas for the treatment and prevention of cataract.