Objective:To study the influence of high frequency oscillatory ventilation (HFOV) on oxygen metabolism and inflammatory factors of patients with acute respiratory distress syndrome (ARDS). Methods: Seventy patients with acute respiratory distress syndrome (ARDS) were randomly divided into the HFOV group (35 cases) and continuous mandatory ventilation (CMV) group (35 cases). The HFOV group accepted HFOV treatment and the CMV group received CMV therapy. Oxygen metabolism and inflammatory factor levels of patients in the two groups were compared before and after treatment. Results: ①After 72 hours of treatment, hemodynamics (heart rate (HR), mean pulmonary arterial pressure (MPAP), APACHE Ⅱ score, multiple organ dysfunction syndrome (MODS) score, oxygen metabolism index (PaO2, PaCO2 and PaO2/FiO2) and inflammatory factor levels (hs-CRP, IL-6, PCT, and TNF-α) in the two groups were significantly improved compared with those before treatment (P < 0.01 or P < 0.05), the above indexes (except for PaCO2) in the HVHF group were more significant than those in the CMV group (P < 0.01 or P < 0.05). ②After 35 days of treatment, the application time of vasoactive drugs and ICU in the HFOV group were shorter than that in the CMV group (all P < 0.05), and no significant differences were found in the mechanical ventilation time and mortality of patients in the two groups (all P > 0.05). There were no complications such as air pressure injury in the two groups. Conclusion: HFOV can not only improve oxygenation function, bu also more effectively reduce the inflammatory response in the lungs, so as to reduce the lung tissue injury, decrease the APACHE Ⅱ score and MODS score, and shorten hospitalization time of vasoactive drug application time and ICU.