The aim of this study was to investigate whether miR-183 could modulate progression of renal fibrosis via targeting SFTPA2 genes. C57BL/6 mice were submitted to unilateral ureteral obstruction (UUO) for inducing renal interstitial fibrosis. Transforming growth factor (TGF)-beta 1-treated HK-2 cells were used as in vitro models of renal fibrosis. miR-183 levels in the cells was monitored by transfecting miR-183 mimic. Expression of miR-183 and SP-A was detected by RT-PCR and Western blotting. Levels of interleukin (IL)-6, IL-1 beta, and tumor necrosis factor (TNF)-alpha in serum and media were measured by ELISA. Compared with the sham group and negative group, expression of SP-A increased while expression of miR-183 decreased in renal tissues of UUO mice. Elevated serum levels of IL-6, IL-1 beta, and TNF-alpha indicated increased inflammation responses in vivo. In TGF-beta 1-treated HK-2 cells, there was also a negative correlation between expression levels of miR-183 and SFTPA2. Over expression of miR-183 in the cells could inhibit SP-A2 expression and reduce levels of inflammatory factors in the culture supernatant. In conclusion, dysregulation of miR-183 and SP-A2 was related with renal fibrosis. The regulatory role of miR-183 was mediated by targeting SFTPA2 genes and affecting inflammation response.