LPCAT2 is a lipid-modifying enzyme that co-localises in lipid rafts with TLR4 and regulates macrophage inflammatory response; however, its effect on TLR4 co-receptor-CD14 is unknown. RAW264.7 cells, a common murine macrophage experimental model, were used to study the effect of LPCAT2 on CD14 expression. The expression of LPCAT2 in RAW264.7 cells was silenced using RNA interference and treated with 100ng/ml of various lipopolysaccharide chemotypes. We found that CD14 expression induced by smooth lipopolysaccharide was significantly decreased (p < 0.05) in RAW264.7 macrophages with LPCAT2 silenced. This study suggests that LPCAT2 regulates CD14 gene and protein expression. This implies that LPCAT2 can regulate CD14-dependent cellular activities.