OBJECTIVE: To investigate the efficacy of nitric oxide (NO) inhaltion on lung function and modulation of inflammation in ventilated premature piglets. METHODS: Premature piglets were obtained at gestation of 101-103 days (89% of full term) with a mean body weight of 870 g. All animals were subjected to mechanical ventilation (PEEP 4-6 cmH2O, Vt 6-8 mL/kg, RR 40-60/min)and randomized into 4 group(n=8 each): Ventilation control, NO inhalation (5-10 ppm), Surfactant (100 mg/kg) or NO plus surfactant. Before and during the ventilation blood gas and lung mechanics were monitored. At the end of the experiment, the lung samples were taken for measuring the NF-κB activity, wet/dry weight ratio and histopathology, and the results were compared with those from 10 non-ventilated premature piglets. RESULTS: The oxygenation index was significantly lower in the NO+surfactant-treated group compared with that of the Control group (2.3±1.9 vs 9.5±7.5, P<0.05). The alveolar aeration in the lungs was similar among the treatment groups. Both NO and NO+surfactant treatments significantly improved the ventilation index. The NO-treated and the Non-ventilated groups had a significantly lower NF-κB activity and wet/dry lung weight ratio compared with the Control group. Neither methemoglobin and NO-2 levels nor inflammatory lung injury was significantly increased in the NO and combined with surfactant-treated groups. CONCLUSIONS: Early treatment with NO alone or combined with surfactant can improve oxygenation and ventilation efficacy without obvious adverse effects on immature lungs of premature piglets. The beneficial effects of NO may be due to the suppresion of NF-κB activity.