In the horse, breeding induces a transient endometrial inflammation. A subset of mares are unable to resolve this inflammation, and they are considered susceptible to persistent mating-induced endometritis PMIE Select seminal plasma proteins cysteine-rich secretory protein-3 (CRISP-3) and lactoferrin have been shown to affect the innate immune response to sperm in vitro. The objective of this study was to determine whether the addition of CRISP-3 and lactoferrin at the time of insemination had an effect on the mRNA expression of endometrial cytokines in susceptible mares after breeding. Six mares classified as susceptible to PMIE were inseminated during four consecutive oestrous cycles with treatments in randomized order of: 1 mg/ ml CRISP-3, 150 mu g/ ml lactoferrin, seminal plasma (positive control) or lactated Ringer's solution (LRS; negative control) to a total volume of 10 ml combined with 1 x 10(9) spermatozoa pooled from two stallions. Six hours after treatment, an endometrial biopsy was obtained for qPCR analysis of selected genes associated with inflammation (pro-inflammatory cytokines interleukin (IL)- 1 beta, IL- 8, tumour necrosis factor (TNF)- alpha, interferon (INF)-gamma, anti-inflammatory cytokines IL- 1RN and IL- 10, and inflammatory- modulating cytokine IL- 6). Seminal plasma treatment increased the mRNA expression of IL- 1 beta (p =.019) and IL- 8 (p =.0068), while suppressing the mRNA expression of TNF (p =.0013). Lactoferrin also suppressed the mRNA expression of TNF (p =.0013). In conclusion, exogenous lactoferrin may be considered as one modulator of the complex series of events resulting in the poorly regulated pro-inflammatory response seen in susceptible mares.