Objective To analyze the effects of Ulinastatin on blood gas indicators and serum tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and intercellular adhesion molecule-1(ICAM-1) of patients with acute respiratory distress syndrome (ARDS). Methods According to the random number table method, 82 patients with ARDS admitted to the Baiyun Branch of Southern Hospital of Southern Medical University from May 2017 to March 2021 were divided into the control group and the observation group, with 41 cases in each group. Patients in both groups were given conventional treatments such as anti-infection and enhanced nutritional support. Patients in the control group were treated with mechanical ventilation on this basis, and patients in the observation group were treated with Ulinastatin on the basis of the control group. Patients in both groups were treated for 7 days. Compared the clinical indicators of the two groups of patients, the blood gas indicators and serum inflammatory factor levels before and after treatment, the occurrence of adverse reactions during the treatment period. Results Compared with the control group, the acute physiological and chronic health status scoreⅡ (APACHEⅡ ) scores of the observation group reduced significantly, and the ventilator support, ICU hospitalization time, total hospitalization time shortened significantly; compared with before treatment, the arterial partial pressure of carbon dioxide (PaCO2) and serum TNF-α, IL-1β, IL-6, ICAM-1 levels of the two groups reduced significantly, and the observation group was significantly lower than the control group; after treatment, the pH value, arterial blood oxygen partial pressure (PaO2), and arterial blood oxygen saturation (SaO2) of the two groups of patients increased significantly and the observation group was significantly higher than the control group (all P <0.05); there was no statistically significant difference in the total incidence of adverse reactions between the two groups during the treatment period (P >0.05). Conclusion Ulinastatin in the treatment of ARDS patients can effectively improve the blood gas indicators, while inhibiting the body's inflammatory response, and has good safety.