Background: Montelukast as an anti-inflammatory drug has a protective effect on the kidney's tissue and also on children with pyelonephritis.Objectives: Therefore, this study aimed at investigating the effect of montelukast on the pyelonephritis symptoms in children. Methods: In this study, 100 children with pyelonephritis were divided into two groups, including the intervention (n = 50) and control (n = 50) groups. Patients in both groups received routine antibiotic therapy and in the intervention group, montelukast (5 mg/day, oral) was prescribed (for 14 days). Finally, the clinical manifestations of the patients were evaluated and compared between two groups. Results: The mean age (± SD) in intervention and control groups was 7.2 (± 0.43) and 7.18 (± 0.43) years, respectively. Analysis of the results showed that the duration of fever (P < 0.0001), dysuria (P < 0.0001), abdominal pain (P < 0.0001) and urgency (P = 0.003) were significantly lower in the intervention group than the control group. Conclusions: Montelukast lead to rapid improvement of clinical manifestations in children with pyelonephritis and may can be used as an effective auxiliary treatment in these patients.