〔Abstract〕 Objective To investigate the effects of miR-203 a-3 p overexpression on pulmonary fibrosis after acute lung injury induced by lipopolysaccharide(LPS) in rats and its possible mechanism. Methods The rat model of pulmonary fibrosis after acute lung injury was established by multiple low-dose injections of LPS. The successfully modeled rats were randomly divided into model group, agomir-negative control group(agomir-NC group) and miR-203 a-3 p agomir group(agomir group), and another control group was set, with 15 rats in each group. One day before modeling and one week after modeling, miR-203 a-3 p agomir was injected by caudal vein for intervention. Two weeks after modeling, the wet/dry specific gravity(W/D) and hydroxyprolinic acid(Hyp) content of lung tissue were determined. The pathological changes and the degree of pulmonary fibrosis of lung tissue were observed by HE staining and Masson staining. The levels of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in broncholveolr lavage fluid(BALF) were determined by ELISA. The expression levels of miR-203 a-3 p and follicle-statin like 1(Fstl1) mRNA in the lung tissues of rats were detected by qRT-PCR. The protein expression level of Fstl1 in lung tissue of rats was detected by Western blot. The targeting relationship between miR-203 a-3 p and Fstl1 was detected by dual luciferase reporting system. Results Compared with control group, the degree of lung injury and pulmonary fibrosis in model group were relatively serious, the W/D value and Hyp content of lung tissue increased(P<0.05), the levels of IL-1β, IL-6 and TNF-α in BALF increased(P<0.05), the expression of miR-203 a-3 p in lung tissue decreased(P<0.05), while the mRNA and protein expression levels of Fstl1 increased(P<0.05). Compared with model group, the degree of lung injury and pulmonary fibrosis were improved in agomir group, the W/D value and Hyp content of lung tissue decreased(P<0.05), the levels of IL-1β, IL-6 and TNF-α in BALF decreased(P<0.05), the expression of miR-203 a-3 p in lung tissue increased(P<0.05), while the mRNA and protein expression levels of Fstl1 decreased(P<0.05). The luciferase reporter gene assay confirmed that Fstl1 was the target gene of miR-203 A-3 p. Conclusion Overexpression of miR-203 a-3 p improves pulmonary fibrosis after LPS-induced acute lung injury, and the mechanism may be related to the targeted down-regulation of Fstl1 expression.