Objective? To investigate the effect of Ulinastatin combined with continuous blood purification on endothelial function and serum inflammatory factor levels in the treatment of acute respiratory distress syndrome (ARDS). Methods According to the random number table method, 120 ARDS patients admitted to Wuhan Asia Heart Hospital from September 2019 to September 2021 were divided into the control group and the observation group, with 60 cases in each group. Patients in both groups were treated with conventional treatment (oxygen therapy, glucocorticoids, maintenance of homeostasis, lung protection, mechanical ventilation and active treatment of primary diseases, etc.), and on these basis, patients in the control group received continuous blood purification treatment (the treament course was 3 d), patients in the observation group were treated with Ulinastatin on the basis of the control group (the treament course was 7 d). The mechanical ventilation time, intensive care unit (ICU) length of stay, acute physiology and chronic health status Ⅱ (APACHE Ⅱ ) score after treatment were compared between thetwo groups; the endothelial function, inflammatory factors, serum calcium binding protein S100A12 and decoy receptor 3 (DcR3) levels were compared between the two groups before and after treatment. Results After treatment, the APACHE Ⅱ score of the observation group was lower than that of the control group, and the mechanical ventilation time and ICU length of stay were shorter than those of the control group; compared with before treatment, exhaled condensate nitric oxide (NO), serum NO and interleukin-10 (IL-10) levels after treatment of the two groups of patients increased, and the observation group was higher than the control group; after treatment, the exhaled condensate endothelin (ET-1) and serum ET-1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), S100A12 and DcR3 levels decreased, and the observation group was lower than the control group (all P<0.05). Conclusion? Ulinastatin combined with continuous blood purification in the treatment of ARDS can effectively shorten the ICU length of stay and mechanical ventilation time, improve the permeability of the vascular endothelium, reduce the body's inflammatory response, correct alveolar edema, relieve the clinical symptoms of the patient and promote the recovery of the patient.