BACKGROUND: Salmonella enterica serovar Typhimurium (ST) is a gram-negative facultative intracellular bacterium with the ability to infect a wide range of hosts. OBJECTIVES: This study aimed to provide a snapshot of the immune responses against ST challenge in primary chicken monocyte-derived macrophages (MDMs) by evaluating the transcriptional changes in inflammatory cytokine interleukin (IL)-1β. METHODS: After preparing blood MDMs, cell monolayers were challenged with ST at a multiplicity of infection of 50. Transcriptional analyses of inflammatory cytokine IL-1β were performed by reverse transcription-quantitative polymerase chain reaction using SYBR Green dye. RESULTS: The results indicated that wildtype ST challenge in avian MDMs favors the differentiation of macrophages toward the alternatively activated M2-like cells through downregulating inflammatory IL-1β. CONCLUSIONS: The findings demonstrated the preferential differentiation of chicken macrophages toward the alterna-tively activated M2-like cells upon ST infection. Further improvement of the existing control measures, such as vaccination and molecular-based immunotherapeutic strategies against poultry salmonellosis requires a better understand-ing of mechanisms involved in the immunomodulatory actions of Salmonella in immune cells in future studie