Background: Chylothorax is a rare disease with a high mortality rate in pediatric patients like newborns and infants. As one of the minimally invasive treatments, chemical pleural pleurodesis has been gradually used in treating pediatric chylothorax patients in recent years. This study explored the feasibility, safety and effect of povidone-iodine chemical pleurodesis (CP) for spontaneous chylothorax in young pediatric patients.Methods: From January 2009 to December 2019 the clinical data of 22 children treated for spontaneous chylothorax at Guangdong Second Provincial General Hospital were retrospectively analyzed. The data included the patients' medical history, clinical manifestations, pleural effusion examinations, treatment methods, and effects and complications. On the basis of conventional conservative treatment and closed thoracic drainage, all the children were treated by CP with povidone-iodine until the pleural effusion was absorbed and the thoracic tube was removed. After discharge from the hospital, each patient was followed up for 1-10 years.Results: Of the 22 children (16 males and 6 females), 3 cases were diagnosed with pleural effusion at prenatal examination, 5 cases had acute respiratory distress at birth, and 6 case had experienced pneumonia repeatedly since birth. All of the children had different degrees of cyanosis and dyspnea. Pleural effusion was diagnosed in all patients by chest X-ray and chest ultrasound after admission (12 cases on the left side, 5 cases on the right side, and 5 cases on both sides). The results of all chyle tests during pleural effusion examination were positive. The mean leukocyte count was (9,278.8±9,504.6)×10 6 /L, the lymphocyte ratio was (83.9±6.1)%, and the mean triglyceride content was (7.18±6.10) mmol/L. All patients were treated with thoracic drainage, diet control, nutritional support, and povidone-iodine CP, among 6 of them with pneumonia on admission received antibiotics. The mean length of stay (LOS) was (36.0±18.2) days. The patients received thoracic drainage for (23.0±15.6) days and pleurodesis (3.0±2.0) times. No serious side effects occurred after pleurodesis, although some patients experienced mild chest pain and low fever. All the patients successfully achieved a clinical cure.Conclusions: Povidone-iodine CP is a safe, effective, and minimally invasive treatment, with high success rate and few complications in young pediatric patients with spontaneous chylothorax.