To observe a therapeutic effect of macrolide antibiotics in children with Pseudomonas aeruginosa pneumonia. Fifty-four cases of children with Pseudomonas aeruginosa pneumonia were randomly divided into an observation group (n=30) and a control group (n=24). The observation group was treated with macrolide antibiotics and cefoperazone/sulbactam. The control group was treated with cefoperazone/sulbactam during a course of 10-14 days. The total effective rate was 93.3% in the observation group, and 58.3% in the control group, and results in the observation group were superior to the control group notably (P>0.05). There were no significant differences in bacterial clearance rate, adverse reaction rate between two groups (P>0.05). The combined application of cefoperazone/sulbactam with macrolide antibiotics to treat Pseudomonas aeruginosa pneumonia in children would be a more effective clinical method.