Purpose. Natural herb has been used for traditional medicine for thousands of years. For this reason, alternative medicine methods affect to domestic animal field. The main purpose of this study was to confirm the regulated proteins after feed additive treatment. Methods. We used total thirty male pigs were used for this experiment. E. coli and Salmonella typhimurium, were used for promote enteritis. Animals were divided into a negative control group, positive control group and test group to determine the effect of an additive mixture on the changes in protein expression in serum. The pigs were given a food supplemented with a natural herbal additive containing immunoglobulin yolksac (IgY) at concentrations 1%. On the 1st week and after eight weeks of feeding, the serums were collected from each group. The changes in the serum proteome as a response to the herbal additive were examined using two-dimensional polyacrylamide gel electrophoresis. Results. A total of 14 differentially expressed protein spots were identified by comparing the protein profiles of the control and additive treated porcine serums. Finally, 7 proteins were detected by MALDI-TOF/MS. Moreover, the proteins detected are involved in a cholesterol control factor, inflammation regulator, Conclusion. These results support of the hypothesis that a natural herbal additive containing IgY can affect the immune regulation system and reduce the pathological process by microbial infections.