Objective To investigate the effect of ulinastatin on severe heat-stroke with acute lung injury induced by severe heat stroke. Methods Thirty severe heat stroke patients were divided into conventional group (n=15) and ulinastatin group (n=15) randomly, with another 80 healthy adults serving as controls. The baseline data such as age, gender, onset period and APACHEⅡ scores were recorded and compared between the two groups on admission. Peripheral leucocyte counts, oxygenation index and Murray scores were determined on the 1st, 3rd and 5th day. The concentration of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and alveolar macrophage supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Western blotting and real-time PCR were used to measure expression of triggering receptor -1 on myeloid cells (TREM-1) on alveolar macrophages. Furthermore, comparison was made in terms of the ventilation period, ICU stay time and mortality in 28 days between the two groups. Results No differences were found in age, gender, onset period and APACHEⅡ scores between the two groups (P>0.05). Compared with the conventional group, peripheral leucocyte counts and Murray scores in the ulinastatin group significantly decreased on the 3rd and 5th day (P<0.05, P<0.01). But oxygenation index was higher in the ulinastatin group than in the conventional group (P<0.05). The concentration of TNF-α and IL-6 in BALF was lower in the ulinastatin group than in the conventional group (on the 3rd day: P<0.05, P<0.01; on the 5th day: P<0.01, P<0.01). The concentration of TNF-α and IL-6 in alveolar macrophage supernatant was lower in the ulinastatin group than in the conventional group (on the 3rd day: P<0.05, P<0.01; on the 5th day: P<0.01, P<0.05). The expression of TREM-1 protein on alveolar macrophages were lower in the ulinastatin group than in the conventional group (on the 3rd day P<0.01; on the 5rd day P<0.05). TREM-1 mRNA was lower in the ulinastatin group than in the conventional group (on the 3rd day: P<0.05; on the 5th day: P<0.05). Eventually, the treatment of ulinastatin shorten ventilation period and ICU stay time (P<0.01, P<0.05). Nonetheless, it failed to show any improvement in terms of the mortality during 28 days (P＞0.05). Conclusion Our study exhibited that ulinastatin had good effect on the heat stroke patients with acute lung injury and it helped reduce the inflammatory reaction of pulmonary tissues. The underlying mechanism of these effects might lie in its ability to reduce heat stroke-induced inflammatory secretion and expression of TREM-1 on alveolar macrophage. DOI: 10.11855/j.issn.0577-7402.2017.04.06