Background <p>Pterygium is a chronic inflammatory condition of conjunctiva. Thrombomodulin (TM) is a glycoprotein involved in the regulation of inflammation. This study investigated TM expression in primary and recurrent pterygium compared to normal conjunctiva, along with its role in pterygium pathogenesis and potential as a therapeutic target for inflammation control.</p> Methods and results <p>Pterygium (10 primary, 10 recurrent) and normal conjunctiva specimens were collected from 20 patients who underwent pterygium excision. TM expression was analyzed using immunofluorescence, western blotting, and real-time quantitative polymerase chain reaction (RT-PCR). Inflammatory markers, including interleukin-6 (IL-6), high mobility group box 1 (HMGB1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and matrix metalloproteinase-1 (MMP-1), were measured. The results showed significantly lower TM expression in pterygium tissues (<i>p</i> &lt; 0.01), with higher TM levels in the head region compared to the body, suggesting a localized inflammatory response. Additionally, macrophage marker F4/80 and neutrophil marker NIMP-R14 were elevated in pterygium tissues. Western blot and RT-PCR confirmed significantly reduced TM expression (<i>p</i> &lt; 0.0001) in primary and recurrent pterygium, with recurrent cases showing even lower levels (<i>p</i> &lt; 0.05). Elevated IL-6, HMGB1, VEGF, bFGF, and MMP-1 levels suggest a strong association between TM downregulation and increased inflammation.</p> Conclusions <p>TM downregulation in pterygium (particularly in recurrent cases) may contribute to chronic inflammation and disease progression. Upregulation of TM at the pterygium head may represent a localized protective response against inflammation. TM supplementation should be explored as a novel therapeutic strategy to mitigate inflammation in pterygium.</p>