Pasteurella multocida (Pm) is an important pathogen causing respiratory disease in beef cattle, often forming mixed infections with Mycoplasma bovis and other pathogens, seriously jeopardizing the healthy development of the cattle industry. Fluoroquinolones and other broad-spectrum antimicrobials are commonly used in clinical treatment of bovine pasteurellosis. However, due to long-term and widespread use of these drugs, this pathogen has developed resistance to multiple antimicrobial agents. The quorum sensing (QS) system serves as a crucial mechanism for bacterial communication and has been confirmed to extensively participate in regulating key biological processes including bacterial virulence expression, biofilm formation, bacterial growth, antibiotic resistance, and symbiosis. Among these, the Type I QS system is primarily found in Gram-negative bacteria and functions mainly through acyl-homoserine lactone signaling molecules. In this study, we added 200 mg/L of the C6 signal molecule and performed transcriptomic, proteomic, and metabolomic sequencing on the sub-inhibitory concentration treatment group (Pm-E1), sub-inhibitory concentration plus C6 treatment group (Pm-E2), and control group (Pm-YQ) to investigate its regulatory mechanism on enrofloxacin（ENR） resistance in Pm.