Objective To investigate the effects of high dose ulinastatin with lung protective ventilatory strategies on respiratory function and prognosis in critical disease patients combined with acute lung injury/acute respiratory distress syndrome. Methods Using retrospective analysis, we involved the critical disease patients combined with ALI/ARDS in ICU of The Second Affiliated Hospital of Anhui Medical University. According to whether they were treated with high dose ulinastatin with lung protective ventilatory strategies or not, the patients were divided into the treatment group and the control group. Then pulmonary vascular permeability index (PVPI), extravascular lung water index (EVLWI), oxygenation index, length of SIRS, length of stay in ICU and APACHE Ⅱ score were observed. Statistic analysis was conducted using SPSS 19.0 software. Results A total of 24 patients were included, 13 cases in the treatment group and 11 cases in the control group. After 72 h, PVPI (P=0.016), EVLWI (P=0.045), length of SIRS (P=0.002), length of stay in ICU (P=0.024) and APACHE Ⅱ score (P=0.002) decreased significantly, while oxygenation index (P=0.004) increased significantly in the treatment group compared with the control group. Conclusion High dose ulinastatin with lung protective ventilatory strategies decreased lung capillary permeability, reduced lung blood capillary leakage and extravascular lung water, resulted in the improvement of lung oxygenation function, decreased of length of stay in ICU and the improvement of prognosis in critical disease patients combined with acute lung injury/acute respiratory distress syndrome.