Cannabidiol (CBD) is a plant-derived cannabinoid that has been predominantly characterized as anti-inflammatory. However, it is clear that immune effects of cannabinoids can vary with cannabinoid concentration, or type or magnitude of immune stimulus. The present studies demonstrate that oral administration of CBD enhanced lipopolysaccharide (LPS)-induced pulmonary inflammation in C57BL/6 mice. The enhanced inflammatory cell infiltrate as observed in bronchoalveolar lavage fluid (BALF) was comprised mainly of neutrophils, with some monocytes. Concomitantly, CBD enhanced pro-inflammatory cytokine mRNA production, including tumor necrosis factor-α (Tnfa), interleukins (IL)-5 and -23 (Il6, Il23), and granulocyte colony stimulating factor (Gcsf). These results demonstrate that the CBD-mediated enhancement of LPS-induced pulmonary inflammation is mediated at the level of transcription of a variety of pro-inflammatory genes. The significance of these studies is that CBD is part of a therapeutic currently in use for spasticity and pain in multiple sclerosis patients, and therefore it is important to further understand mechanisms by which CBD alters immune function.