Contents: Endometrosis is a degenerative chronic process, characterized by paramount fibrosis development in mare endometrium. This condition is one of the major causes of subfertility/infertility in mares. As in other organs, fibrosis might be a pathologic sequel of many chronic inflammatory diseases. However, aetiology and physiopathologic mechanisms involved in endometrial fibrosis are still controversial. This review presents new hypotheses based on our newest data. As the first line of innate immune defence, systemic neutrophils arrive in the uterus at mating or in the presence of pathogens. A novel paradigm is that neutrophils cast out theirDNAin response to infectious stimuli and form neutrophil extracellular traps (NETs). We have shown that bacterial strains ofStreptococcus zooepidemicus, Escherichia coliorStaphylococcus capitis, known to cause endometritis in mares were able to induceNETs releasein vitroby equinePMNto different extents. An intriguing dilemma is the dual action ofNETs. WhileNETs play a desirable role fighting micro‐organisms in mare uterus, they may also contribute to endometrial fibrosis. A long‐termin vitroexposure of mare endometrium explants toNETs components (myeloperoxidase, elastase and cathepsin G) up‐regulated fibrosis markersTGFβand Tissue inhibitor of metalloproteinase (TIMP‐1). Also, pro‐fibrotic cytokines regulated collagen deposition and fibrosis. Changes in expression of connective tissue growth factor (CTGF), interleukins (IL)1‐α,IL‐1β,IL‐6 and receptors in endometrium with different degrees of fibrosis and/or inflammation were observed. A putative role ofCTGF,ILandNETs components in endometrosis development should be considered. Additionally, we speculate that in sustained endometritis in mares, prostaglandins may not only cause early luteolysis or early pregnancy loss, but may also be related to endometrial fibrosis pathogenesis by stimulating collagen deposition.