Objective To observe the effect of different administration routes of bovine lung surfactant on severe neonatal meconium aspiration syndrome (MAS).Methods This study is a prospective study, selecting 85 children with MAS admitted in the First People's Hospital of Shangqiu City between March 2021 and June 2023 as the study subjects. They were randomly divided into a conventional group (42 cases) and a dual pathway group (43 cases) using computer randomization. The conventional group received mechanical ventilation combined with tracheal instillation of bovine lung surfactant, while the dual pathway group received mechanical ventilation combined with bronchoalveolar lavage and tracheal instillation of bovine lung surfactant. The changes in inflammatory factors, blood gas indicators, vascular endothelial function, recovery after treatment, and incidence of complications between the two groups of children were compared.Results After treatment, the levels of IL-6, IL-8, and IL-10 in the dual pathway group were 114.45±10.27 ng/mL, 60.45±10.31 pg/mL, and 45.15±10.27 ng/mL, lower than the conventional group (121.36±10.25 ng/mL, 65.27±10.36 pg/mL, and 50.33±10.24 ng/mL) (P<0.05). The PO₂ and SaO₂ levels in the dual pathway group were 92.44±10.45 mmHg and 95.18%±5.26%, higher than the conventional group (87.32±10.46 mmHg and 92.55%±5.46%) (P<0.05). PCO₂ in the dual pathway group (40.24±10.33 mmHg) was lower than that of the conventional group (45.11±10.19 mmHg) (P<0.05). The NO in the dual pathway group (23.25±5.77 ppb) was higher than the conventional group (20.47±5.16 ppb), while the ET-1 (50.62±10.39 ng/L) was lower than the conventional group (55.47±10.28 ng/L) (P<0.05). The ventilation time, oxygen therapy time, and hospitalization time of the dual pathway group were 3.36±0.24 days, 6.65±1.33 days, and 10.33±2.26 days, lower than the conventional group (4.18±1.77 days, 8.12±2.54 days, and 14.42±4.15 days) (P<0.05). The incidence of complications in the dual pathway group was 9.30% (4/43), lower than that in the conventional group [23.81% (10/42)](P<0.05).Conclusion The dual pathway administration of bovine lung surfactant can effectively alleviate the inflammatory response and blood gas indicators in children with MAS, which has a positive significance in reducing vascular endothelial cell damage, accelerating the recovery process, and reducing the risk of complications.