Lactoferrin (LF) is an estrogen-regulated glycoprotein with well-described antibacterial and immunomodulatory properties. The present study is the first report on LF expression in horse endometrial specimens. Mares chosen for the study were either resistant or susceptible for persisting mating-induced endometritis (PMIE) during the natural ovulatory cycle and in early pregnancy. Our investigations included immunostaining for LF protein and CD18, a leukocyte marker, as neutrophils are a possible source for LF in the endometrium. Quantification of LF mRNA was performed by use of real-time RT-PCR. This study demonstrated that LF protein in equine endometrium was expressed in glandular and luminal epithelium and in neutrophils. Similar to other mammalian species, the level of endometrial LF transcription in the mare was modulated according to the stage of the estrus cycle and was 5500-fold higher during estrus compared with diestrus and early pregnancy. The endometria from mares susceptible for PMIE and delayed uterine clearance exhibited an increased LF transcription during all stages of the estrus cycle that reached statistical significance in proestrus. In the endometria of mares susceptible for PMIE the upregulated LF mRNA expression was not associated with a higher number of CD18 positive leukocytes but correlated with the number of uterine glands. Enhanced LF transcription within the endometrial epithelium might therefore be a response to recurrent persisting inflammation following insemination in mares with delayed uterine clearance.