Background: Lysophosphatidylcholine (LPC) is generated through the hydrolysis of phosphatidylcholine (PC) by phospholipase A2 and is converted back to PC by lysophosphatidylcholine acyltransferase 1 (LPCAT1). Elevated levels of (LPC) are known to play a pathogenic role in the inflammatory injury of asthma. However, the role of LPCAT1 in asthma has not yet been reported. Objective: To determine whether the exogenous expression of LPCAT1, delivered by using a recombinant lentiviral vector, could attenuate airway inflammation in asthmatic mice. Methods: Recombinant lentivirus carrying cDNA encoding LPCAT1 (Lenti-LPCAT1), or EGFP (Lenti-EGFP) as a control, was constructed. BALB/c mice were sensitised with ovalbumin (OVA), and intratracheally pre-treated with an endobronchial administration of the recombinant lentivirus intratracheally 72 hours before the first challenge. After the last OVA challenges, the mice were assessed for airway inflammation, airway hyper-responsiveness and lipid levels. Results: Lenti-LPCAT1-infected HEK293T cells expressed exogenous recombinant LPCAT1 protein that showed high activity of the LPC acyltransferase. OVA sensitisation and challenge significantly increased the levels of saturated species LPC 16: 0 and LPC 18: 0 levels in the bronchoalveolar lavage fluid (BALF) compared with wild-type mice respectively. The intratracheal Lenti-LPCAT1 instillation obviously down-regulated the OVA-induced release of LPC 16: 0 and LPC 18:0. Treatment with Lenti-LPCAT1 ameliorated OVA-induced airway hyper-responsiveness and reduced airway eosinophilia infiltration in lung tissue. Furthermore, the secretion of eotaxin and Th2-associated cytokines IL-5 and IL-13 were inhibited in BALF. The level of OVA-specific IgE in serum was suppressed. Conclusions: These results suggested that the exogenous expression of LPCAT1 may attenuate eosinophil inflammation in the airway by down-regulating the LPC 16: 0 and LPC 18: 0 BALF levels in asthmatic mice.