An UHPLC-ESI-Q Exactive HF MS-based lipidomics method was successfully applied to profile various lipids from the plasma and lungs of mice intranasally challenged with lipopolysaccaride (LPS). Response trends of lipids to LPS were graphically represented by variable importance in projection (VIP) plot, heat map, and bar plot. As a result, 77 differential lipids in the lung and 13 differential lipids in the plasma were identified by comparison between healthy and LPS- induced mice. These results revealed the correlation between inflammation and lipids metabolism. The differentially regulated lipids could also be potentially used as biomarkers for inflammation.