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Aims: Pathophysiology of neonatal meconium aspiration syndrome (MAS) is complex and includes airway obstruction, dysfunction of pulmonary surfactant, and induction of local inflammation followed by formation of lung edema. Standard therapy of MAS is based on ventilatory support and administration of exogenous surfactant, but in serious cases it can be ineffective. The reduced effect of therapy is caused by generation of inflammation, signalling through TLR4/MD-2 CD14 complex, and increasing production of inflammatory markers, reactive oxygen species and proteolytic enzymes which can inactivate and degrade surfactant (Salvesen et al, 2010). Therefore, an agent affecting pro-inflammatory transcription factors, budesonide, was used to inhibit expression of inflammatory markers, as we expected that budesonide may improve effectiveness of surfactant therapy in MAS (Mokra et al, 2007). Methods: In anesthetized and oxygen-ventilated New Zealand rabbits, respiratory failure was induced by intratracheal administration of meconium. Animals were divided into four groups: without therapy (Mec), with surfactant therapy (Surf), with budesonide therapy (Bud), and with combined surfactant and budesonide therapy (Surf+Bud). Saline was given instead of meconium in the control group (Sal). Blood gases, ventilatory pressures, and other respiratory parameters were registered before and after meconium instillation, and 0.5, 1, 2, 3, 4, 5 hours after the therapy. After sacrificing the animals, inflammation markers were determined in lung tissue and plasma. Lung edema expressed as wet/dry weight (W/D) ratio, oxidative damage of lipids (thiobarbituric acid-reactive substances, TBARS) and proteins (3-nitrotyrosine), levels of interleukins (IL)-1b and -8 and TNFα in plasma, and mRNA expression of IL2, -10, -13, and TNFα were analysed. Results: Combined Surf+Bud therapy rapidly improved oxygenation and lung function parameters compared with other groups (p<0.05) since 30 min of the therapy and this improvement persisted till the end of experiment. Combined therapy reduced both W/D ratio and TBARS (p<0.05 vs. Mec group). All kinds of therapy decreased levels of IL-1b and IL-8 (p<0.5 vs. Mec) in plasma, but effect of Surf+Bud was superior (IL-1b p<0.009, IL-8 p<0,003). Similarly, the most potent effect of therapy on mRNA expression of IL-13 and TNFα was observed in the Surf+Bud group. Conclusions: Combined surfactant and budesonide therapy had positive and long-term effects on lung functions and reduced lung edema, oxidative damage of lipids and proteins, and inflammation expressed by decrease in interleukins on protein and mRNA levels. The results indicate that addition of anti-inflammatory agent to surfactant therapy may reduce surfactant inactivation and enhance effectiveness of the therapy of MAS. [ABSTRACT FROM AUTHOR]