Abstract Introduction: Macrophages play a key role in inflammatory diseases. We aimed to identify long noncoding RNAs that regulate pro-inflammatory activation of human macrophages. Methods: We performed human lncRNA microarray analysis in LPS-stimulated primary human macrophages. We then carried out loss-of-function and gain-of-function experiments, luciferase reporter assays, RNA pulldown, RNA immunoprecipitation, and mouse endotoxemia studies, including humanized mouse models.