[Abstract] Objective To investigate the effect of tracheal administration of Pulmonary Surfactant and Budesonide on complications of respiratory distress syndrome in premature infants. Methods Premature infants with respiratory distress syndrome admitted to the Department of Neonatology of Huizhou Central People’s Hospital from October 2021 to May 2022 were selected for a retrospective study, and divided into the experimental group (n=33) and the control group (n=30) according to the different treatment methods. The control group was treated with Pulmonary Surfactant, and the experimental group was treated with Pulmonary Surfactant and Budesonide. The ventilator use time, total oxygen duration, hospital stay and complications were compared between the two groups. Results The total time of ventilator use, total oxygen duration and hospital stay in the experimental group were lower than those in the control group, and the differences were statistically significant (P < 0.05). The incidence of intracranial hemorrhage in the experimental group was lower than that in the control group, and the difference was statistically significant (P < 0.05). The severity of bronchopulmonary dysplasia in the experimental group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Conclusion Endotracheal administration of Pulmonary Surfactant and Budesonide can improve the complications of respiratory distress syndrome in very low birth weight premature infants and improve the prognosis of the lung, which is worthy of clinical application.