Objective To investigate the effect of celecoxib (CXB) on extracellular matrix (ECM) remodeling in a model of autosomal dominant polycystic kidney (ADPKD). Methods Fifty seven Han: SPRD heterozygous (Cy/+) rats were randomly divided into 3 groups: control group, small dosage CXB group (3 mg&#8226;kg-1&#8226;d-1) and large dosage CXB group (10 mg&#8226;kg-1&#8226;d-1). Renal cystic index(CT), fibrosis index and inflammatory cells infiltration in interstitium were analyzed. The mRNA expression of typeⅣ collagen (COLⅣ), matrix matalloproteinase-2 (MMP-2), metalloproteinase-2 tissue inhibitor (TIMP-2) and transforming growth factor β1 (TGF-β1) was detected by real-time PCR. The co-expression of COLⅣ, MMP-2, TIMP-2, TGF-β1 and proliferating cell nuclear antigen (PCNA) was analyzed by double immunofluorescence labeling technique and laser scanning confocal microscopy. The protein expression of TGF-β1 was detected by Western blotting. Results CT (42.90±6.56 & 47.10±7.28 vs 64.80±6.71, all P<0.05), fibrosis index (11.20±2.63 & 10.10±3.30 vs 16.30±4.16, all P<0.05) and inflammatory cells infiltration (2.60±0.26 & 2.80±0.31 vs 3.70±0.33, all P<0.05） in interstitium all decreased in small and large dosage group compared to control group. COLⅣ，TIMP-2 and TGF-β1 mRNA level decreased in both small and large dosage groups as well. Contrarily MMP-2 mRNA level increased in both groups(all P<0.05). The co-expression of COLⅣ distributed widely in tubulointerstitial area in control group but only few in small (20.30±5.11 vs 61.40±4.51, P<0.01) and large dosage group (27.50±6.73 vs 61.40±4.51, P<0.05）. MMP-2/TIMP-2 ratio increased in smalll dosage group (4.88±1.52 vs 0.35±0.13, P<0.05) and large dosage group (3.63±1.67 vs 0.354±0.13, P<0.05) as compared to control group. Western blotting showed the expression of TGF-β1 decreased in both small and large dosage groups (all P<0.05). Conclusion CXB can inhibit tubulointerstitial fibrosis in Han:SPRD rats by inhibiting the expression of TGF-β1, promoting COLⅣ degradation and increasing MMP-2/TIMP-2 ratio.