〔Abstract〕 Objective To investigate the effect of hypoxia on miR-486 expression in human embryonic lung fibroblast MRC5 cells and identify mechanism of miR-486 in pulmonary fibrosis induced by hypoxia. Methods MRC5 cells were treated with hypoxia. Quantitative real-time PCR(qRT-PCR) was applied to detect the expression of miR-486,fibronectin(FN) and alpha smooth muscle actin(α-SMA),and Western blot was used to measure the expression of p-SMAD2 and GAPDH in MRC5. Lentivirus was used to mediate the overexpression or inhibition of miR-486 in MRC5 cells. Then,qQRT-PCR was used to detect the expression of miR-486,FN,α-SMA,Collagen Ⅰ and Collagen Ⅲ,and Western blot was used to measure the p-SMAD2 and GAPDH expression. Results Hypoxia inhibited the expression of miR-486 and promoted the FN,α-SMA and p-SMAD2 expression. MiR-486 overexpression successfully increased miR-486 expression and inhibited FN,α-SMA,Collagen Ⅰ,Collagen Ⅲ and p-SMAD2 expressions. MiR-486 knockdown upregulated the expressions of FN,α-SMA,Collagen Ⅰ,Collagen Ⅲ and p-SMAD2. Conclusion MiR-486 may regulate the pathogenesis of pulmonary fibrosis induced by hypoxia through targeting SMAD2.