Abstract: Objectives: The efficacy of microencapsulated Na-butyrate (NaB) supplementation for reducing Salmonella enteritidis (S. enteritidis) infection was investigated. Methodology: One day old broiler chicks (n = 200) were allotted into 4 equal groups. At 2nd day of age, birds of groups 3 and 4 were challenged by crop gavage with 5x108 CFU mL–1 of S. enteritidis. Groups 2 and 3 were supplemented with NaB diet while 1 and 4 were fed on a plain ration without treatment. Scanning Electron Microscopy (SEM) of re-isolated S. enteritidis of challenged NaB treated broilers revealed broken cells with morphological changes in comparison with untreated challenged group, however, Transmission Electron Microscopy (TEM) showed several lipids like bodies that barely detected in untreated group. Results: Results from Polymerase Chain Reaction (PCR) analyses revealed that S. enteritidis strain from untreated challenged control harbored virulence genes invA, stn and pefA with incidence rate of 100%. While, NaB supplementation resulted in detection of 100% of invA gene and only 66.6% of pefA and stn genes. Gut integrity of NaB supplemented groups showed significant (p≤0.05) increase in villi height and villus height: crypt depth ratio and had positive effect in maintenance of healthy intestinal epithelial cells. Conclusion: NaB supplement is effective in reducing S. enteritidis in chickens.