Objective: To study the effect of ulinastatin combined with antibiotics on systemic inflammatory response and stress hormone secretion in patients with acute severe pneumonia. Methods: A total of 78 patients with acute severe pneumonia in our hospital between December 2014 and January 2017 were randomly divided into routine group and ulinastatin group, each with 39 cases. Routine group were treated with conventional antibiotics, ulinastatin group were treated with ulinastatin and antibiotics, and the treatments lasted for 2 weeks. The differences of serum acute phase proteins, inflammatory factors and stress hormones were compared between the two groups before and after treatment. Results: Before treatment, there were no significant differences in serum contents of acute phase proteins, inflammatory factors or stress hormones between the two groups. After 2 weeks of treatment, serum acute phase protein prealbumin (PA) content in ulinastatin group was higher than that in routine group whereas C-reactive protein (CRP) content was lower than that in routine group; serum inflammatory cytokines interleukin-1β (IL-1β), interleukin-2 (IL-2) and interleukin-6 (IL-6) contents in ulinastatin group were lower than those in routine group; serum stress hormones NE, Cor and AngII contents in ulinastatin group were lower than those in routine group. Conclusion: Ulinastatin combined with antibiotics for acute severe pneumonia can inhibit the systemic inflammatory response and stress resp