Purpose: BALB/c mice are resistant to Pseudomonas aeruginosa (P. aeruginosa ) keratitis and bacterial killing/stasis requires nitric oxide (NO). NO regulation in the cornea is unknown and was tested in this model. Methods: Nitrite detection, IFN-gamma-knockout mice, TNF-alpha neutralization, ELISA, aminoguanidine (AG) treatment, MPO, and plate counts were done. Results: Evidence shows (i) without IFN-gamma, nitrite levels are elevated, (ii) neutralization of TNF-alpha does not change nitrite levels, and (iii) absence of IFN-gamma and reduced NO synergistically increases disease progress and upregulates pro-inflammatory cytokines, PMN number, and bacterial load. Conclusion: IFN-gamma regulates NO levels, and synergistic interaction between the two regulates disease outcome in resistant mice.