Background: Lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria induces an intense inflammatory response in pigs. Long noncoding RNAs (lncRNAs) are emerging as key regulators in inflammation and immunity. However, their functions and profiles in LPS-induced inflammation in pigs are largely unknown. In this study, we profiled global lncRNA and mRNA expression changes in porcine peripheral blood mononuclear cells (PBMCs) treated with lipopolysaccharide (LPS) using lncRNA-seq technique. Result: Totally 43 differentially expressed (DE) lncRNAs and 1082 DE mRNAs were identified in the porcine PBMCs after LPS stimulation. Functional enrichment analysis on DE mRNAs indicated that these genes were involved in inflammation-related signaling pathways, including cytokine-cytokine receptor interaction, TNF, NF-κB, Jak-STAT and TLR signaling pathways. Additionally, co-expression network and function analysis identified the potential lncRNAs related to inflammatory response and immune response. The expression of eight lncRNAs (ENSSSCT00000045208, ENSSSCT00000051636, ENSSSCT00000049770, ENSSSCT00000050966, ENSSSCT00000047491, ENSSSCT00000049750, ENSSSCT00000054262 and ENSSSCT00000044651) was validated in the LPS- treated and non-treated PBMCs by quantitative real-time PCR (qRT-PCR). In LPS-challenged piglets, we identified that three lncRNAs (ENSSSCT00000051636, ENSSSCT00000049770, and ENSSSCT00000047491) were significantly up-regulated in liver, spleen and jejunum tissues after LPS challenge, which revealed that these lncRNAs might be important regulators for inflammation .Conclusion: This study provides the first lncRNA and mRNA transcriptomic landscape of LPS-mediated changes in porcine PBMCs. These findings may provide potential insights into lncRNAs involved in regulating immune and inflammation in pigs.