Lipopolysaccharide (LPS), a core part of gram-negative bacteria, is crucial for inducing an inflammatory response in living things. In the current study, we used LPS from Salmonella to stimulate chicken macrophages (HD11). Proteomics was used to investigate immune-related proteins and their roles further. Proteomics investigation revealed 31 differential expression proteins (DEPs) after 4 hours of LPS infection. 24 DEPs expressions were up-regulated, while seven were down-regulated. In this investigation, ten DEPs were mainly enriched in S. aureus infection, complement, and coagulation cascades, which were all implicated in the inflammatory response and clearance of foreign pathogens. Notably, complement C3 was shown to be up-regulated in all immune-related pathways, indicating that it is a potential protein in this study. This work contributes to a better understanding and clarification of the processes of Salmonella infection in chickens. It might bring up new possibilities for treating and breeding Salmonella-infected chickens.