The action of Interleukin-6 (IL-6) impacts female reproduction. Although IL-6 was recently shown to inhibit cilia activity in human fallopian tubes in vitro, the molecular mechanisms underlying IL-6 signaling to tubal function remain elusive. Here, we investigate the cellular localization, regulation, and possible function of two IL-6 receptors (IL-6R and gp130) in mouse and human fallopian tubes in vivo. We show that IL-6R is restricted to the cilia of epithelial cells in both mouse and human fallopian tubes. Exogenous 17-estradiol (E₂), but not progesterone (P₄), causes a time-dependent decrease in IL-6R expression which is blocked by the estrogen receptor (ER) antagonist ICI 182,780. Exposure of different ER-selective agonists, PTT or DPN, demonstrated an ER subtype-specific regulation of IL-6R in mouse fallopian tubes. In contrast to IL-6R, gp130 was detected in tubal epithelial cells in mice but not in humans. In humans, gp130 was found in the muscle cells and was decreased in the periovulatory and luteal phases during the reproductive cycles, indicating a species-specific expression and regulation of gp130 in the fallopian tube. Expression of tubal IL-6R and gp130 in IL-6 knockout mice was found to be normal; however, E₂ treatment increased IL-6R, but not gp130, in IL-6 knockout mice compared to wild-type mice. Furthermore, expression levels of IL-6R, but not gp130, decreased in parallel with estrogenic accelerated oocyte-cumulus complex (OCC) transport in mouse fallopian tubes. Our findings unveil a potential role for cilia-specific IL-6R in the regulation of OCC transport and suggest an estrogen-regulatory pathway of IL-6R in the fallopian tube.