Objectives: The present study explored the possible protective effect of IgY on PA lung infection in vivo. Methods: In vivo model of acute lung infection: Balb/c mice were anaesthetized with isoflurane and PAO1 vaccine strain ± specific (S-IgY) or control (C-IgY) was inoculated intranasally. Mice were sacrificed after 2, 6 and 24h and lungs removed aseptically, weighted and suspended in PBS. A blinded observer engaged a clinical scoring system (0−5) of the mice. Lungs were homogenized, serially diluted and cultured on Conradi-Drigalski medium for estimation of bacterial load. Results: Relative lung weight: Lung weights in the S-IgY treated group were significantly reduced 24h post-infection compared to PBS controls (p< 0.03). No significant difference between C-IgY and PBS groups were observed. Clinical symptom score: The clinical score was significantly lower in the S-IgY group compared to controls after 6h (C-IgY: p< 0.05, PBS: p< 0.05). After 24h the clinical score in the S-IgY was reduced additionally compared to controls (PBS: p< 0.002, C-IgY: p< 0.04). No significant difference between C-IgY and PBS groups were observed. Quantitative bacteriology: The bacterial load of S-IgY treated mice was significantly reduced 2h post-infection compared to PBS group (p< 0.02) and C-IgY (p< 0.03) and further reduced 6h post-infection compared to both control groups (PBS: p< 0.0001, C-IgY: p< 0.03). After 24h the lung bacteriology in S-IgY treated mice was reduced by 2 logs compared to PBS (p< 0.0001) and C-IgY (p< 0.0002) groups. Conclusion: The present results imply that anti-PA IgY antibodies protects against PA lung infection due to readily bacterial clearance in the airways.