The intrauterine device (IUD) is an effective method of birth control. However, IUD-induced uterine bleeding is a major side-effect and always causes inconvenience, sometimes even anaemia. It has been reported that oral administration of indomethacin could can reduce IUD-induced uterine bleeding. In the present study, we investigated whether indomethacin-releasing copper IUD (IR-Cu-IUD) can prevent insertion-induced uterine bleeding and its mechanism. Nine healthy volunteers of reproductive age were selected for the study. Endometrial tissues were collected at same menstrual stage prior to and 3-6 months after IR-Cu-IUD insertion. Endometrial morphology, cell proliferation/differentiation, morphometry and activity of complement Factor VIII were examined. No significant difference was found in any of the parameters examined in the same patients, both prior to and after IR-Cu-IUD insertion. By comparison with data previously obtained from the patients who had Cu-IUD insertions, it is clear that IR-Cu-IUD markedly reduced IUD-induced uterine bleeding and this reduction is primarily contributed by the anti-inflammatory action of indomethacin.