The present study describes the effect of a single dose of dexamethasone administered to mares at time of breeding. In an initial experiment, the authors investigated safety of treatment. In a second experiment the effect of treatment on the uterine environment, fetal development and pregnancy outcome was examined. In the final part of the study, mares susceptible to persistent mating induced endometritis were identified, by means of a risk factor score system and the effect of treatment evaluated. Results indicated that dexamethasone administered at breeding time did not negatively impact on mares medical and reproductive traits. A reduced inflammatory response was observed post-mating in treated versus control mares and mares with multiple risk factors for susceptibility to persistent mating induced endometritis showed improved pregnancy rates following treatment. The authors concluded that a single dose of dexamethasone administered at the time of breeding is safe and can be used to modulate the uterine inflammatory response to breeding in susceptible mares.