Objective Intravenous azithromycin (AZM) has been widely used in children worldwide, but there still remains much concern regarding its off-label use, which urgently needs to be regulated. Therefore, we developed a rapid advice guideline in China to give recommendations of rational use of intravenous AZM in children. Methods This guideline focuses on antimicrobial therapy with intravenous AZM in children. The Delphi research method was used to select questions. A systematic literature review was also conducted. Data were pooled and ranked according to the GRADE system. Recommendations were developed based on expert clinical experience, patients' values and preferences, and evidence availability. After an external review, the recommendations were revised and approved. Results This guideline included eighteen recommendations that covered four domains: (a) Indications: the treatment of pneumonia caused by atypical but common pathogens, such as Mycoplasma pneumoniae, Chlamydia trachomatis or Chlamydophila pneumoniae and Legionella pneumophila, more typical bacteria as well as the treatment of bronchitis of presumed bacterial aetiologies; (b) Usage and dosage: administration route, infusion concentrations, treatment duration, course of sequential treatment, and dosage stratified by age; (c) Adverse reactions and treatment: the management of gastrointestinal reactions, arrhythmias, pain or phlebitis at the infusion site, and anaphylaxis; and (d) Special population: children with renal or liver dysfunction, congenital heart disease, and obesity. This guideline will hopefully help promote a rational use of intravenous AZM in children worldwide. Conclusion This guideline has summarised the evidence and has developed recommendations on the use of intravenous AZM in children worldwide. Further attention and well-designed researches should be conducted on the off-label use of intravenous AZM in children.