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Background: COPD is an important and increasing cause of mortality, it was estimated to be the fifth leading cause of death. The aim of this work is to study the value of hyaluronic acid (HA) in patients with chronic obstructive pulmonary disease (COPD) and follow up its level with medications in these patients. Patients and methods: This cross-sectional study was carried out in chest department at Benha university hospitals, the samples were collected from patients in the period from Mars 2019 to December 2020. All subjects underwent history talking and clinical examination, plain chest x-ray (postero-anterior) and (left-lateral) view and PFT (spirometery) before and after bronchodilator and it will be repeated at 3 and 6 months with the assay HA Results: there was statistically significant decrease in Hyaluronic acid in visit two than visit one, and in visit three than visit one and two, and there was statistically significant difference between the controls and the two sub groups as regards Hyaluronic acid, where control is the lowest then subgroup 1 then subgroup 2 in the three visits. Conclusion: The significant decreasing of HA level at patients with COPD may be a marker of the effectiveness of anti-inflammatory treatment (AIT).