Objective To explore the effect of intervention of downregulating miR-192 on post-injury renalinterstitial fibrosis in rats with unilateral ureteral obstruction (UUO), and the mechanism involved. Methods Forty-fivehealthy male SD rats were randomly divided into a sham group, model group, and antagomir-192 group. The rat model ofrenal interstitial fibrosis was constructed in all rats (except the sham group) through left ureter ligation. Rats in theantagomir-192 group were given tail vein injection of antagomir-192 on days 1, 7, and 14 after surgery, while rats in thesham group and model group were given tail vein injection of an equivalent amount of normal saline. All rats were sacrificedon day 21 after surgery. Changes in miR-192 expression in the obstruction-side renal tissues were detected through real-timefluorescence quantitative PCR (qRT-PCR). Blood was collected from the heart to determine the serum levels of blood ureanitrogen (BUN) and creatinine (Cr) in rats, and the pathological changes in the obstruction-side renal tissues wereobserved using HE staining. Moreover, the obstruction-side renal interstitial collagen fiber deposition rate was calculatedusing Masson staining, and western blotting was performed to detect the changes in expression of epithelial-mesenchymaltransition (EMT)-related markers, E-cadherin, α-smooth muscle actin (a-SMA), vimentin, and collagen I, in theobstruction-side renal tissues. Results Compared with the sham group, the miR-192 expression level in renal tissues,serum BUN and Cr levels, renal interstitial injury score, and renal interstitial collagen fiber deposition rate in the modelgroup were markedly upregulated ( P <0. 01); E-cadherin protein expression in renal tissues was notably downregulated ( P <0. 01); while α-SMA, vimentin, and collagen I protein expression was dramatically elevated ( P <0. 01). Compared withthose in the model group, the miR-192 expression level in renal tissues, serum BUN and Cr levels, renal interstitial injuryscore, and renal interstitial collagen fiber deposition rate in the antagomir-192 group were remarkably reduced ( P <0. 01); E-cadherin protein expression in renal tissues was evidently increased ( P < 0. 01); while α-SMA, vimentin, andcollagen I protein expression was dramatically decreased ( P < 0. 01). Conclusions miR-192 expression is elevated inrenal tissues of rats with renal interstitial fibrosis, and downregulating miR-192 can suppress renal interstitial fibrosis in UUO rats, thus exerting a protective effect.