Purpose: Prostaglandin E2 (PGE2) is increased in the lower respiratory tract of patients with COPD. Hepatocyte growth factor (HGF) plays a role in modulating epithelial cell proliferation. In some mesenchymal cells, PGE2 modulates HGF production. This study was to see if PGE2 modulates HGF production and to determine the specific receptors involved. Methods: Human fetal lung fibroblasts (HFL-1) were cultured in Dulbecco`s Modified Eagle`s Medium DMEM) with 10% fetal calf serum. For stimulation, media were changed to DMEM without serum and supplemented with PGE2 or specific agonists and antagonists for each of the four E-prostanoid (EP) receptors. Media were harvested and assayed for HGF by ELISA.Forskolin, KT-5720 (PKA antagonist), and wortmannin were treated to investigate the downstream pathway. Results: Release of HGF was stimulated by PGE2 (p＜0.05). The effect was greater as cells became confluent in culture over 10 days. Both PGE2 and EP2 agonist stimulated HGF release in a concentration dependent manner. EP2 antagonist inhibited the stimulatory effect of PGE2 and EP2 agonist. The other EP agonists and EP antagonists did not alter HGF release.Forskolin treatment also enhanced HGF release (p＜0.05). KT-5720 inhibited HGF release (p＜0.05) but wortmannin did not. Conclusion: HGF production in HFL-1 is stimulated by PGE2 acting on EP2 receptor. Forskolin has a similar effect suggesting that the effect is mediated by modulation of cAMP. The pathway of HGF release through the stimulation by PGE2 is a potential target to modulate lung tissue repair.