Inflammatory diseases, such as bovine respiratory disease complex (BRD), are the most frequently observed diseases in dairy and feedlot cows, and most common cause of economic loss. Calves are highly sensitive to the component of the gram-negative bacterial envelope known as LPS or endotoxin. The acute-phase response to endotoxin may regulate transcription factors, such as nuclear factor kappa B (NF-kB) or STAT-3, and the release of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6), from neutrophils and monocytes/macrophages. Many studies have reported NF-kB transcription factors and signaling pathways to be the central coordinators in immune and inflammatory responses, and STAT-3 was found to regulate the expression ofnumerous genes in response to cellular stimuli. The activation of and interaction between NF-kB and STAT-3 are vital for inflammatory control, but it is unknown how endotoxin affects the NF-kB family and STAT-3 in calves. In this study, we examined sequential changes in mRNA levels of TLR-4, NF-kB 1, NF-kB 2, IL-6, and STAT-3 in polymorphonuclear leukocytes (PMNs) and the liver using an endotoxin challenge model.