Abstract: Objective To investigate whether complement C3 is involved in the process of post-injury fibrosis after ischemia-reperfusion induced acute kidney injury（IR-AKI）. Methods The IR-AKI and post-injury fibrosis model was established by left renal artery clamping with micro-arterial clip for 30 minutes, and resecting the right kidney one week later in C57 BL/6 mice. Fifty successful mice were randomly divided into 5 groups to detect the concentrations of complement C3, interleukin（IL） 1, IL-6 and transforming growth factor（TGF）-β₁ and the protein expression of these indexes in renal tissue by enzyme-linked immunosorbent assay（ELISA） and Western blot on day 0, 3, 7, 14 and 28 respectively. In addition, twenty C57 BL/6 mice and twenty gender-and age-matched complement C3 knockout(C3^-/-) mice were randomly divided into IR-AKI and post-injury fibrosis（chronic kidney disease, CKD） group and sham-operation group respectively, namely C57 BL/6-AKI-CKD group, C3^-/--AKI-CKD group, C57 BL/6-sham group, C3^-/--sham group. In the sham group, only the left renal artery were isolated without blocking the blood flow.After 28 days, the 24 h urine protein, serum creatinine（Scr） and blood urea nitrogen（BUN） were detected; HE and Masson staining were performed to observe glomerulus, renal tubules and renal fibrosis; the concentrations of complement C3, IL-1, IL-6 and TGF-β₁ of renal tissue were measured by ELISA, and the expression of complement C3, IL-1, IL-6, and TGF-β₁ protein were detected by Western blot. Results After AKI, the expression of renal complement C3, IL-1, IL-6 and TGF-β₁ increased in a time-dependent manner and reached to the peak on the 7 th day. Compared with the sham group, on the 28 th day, the ScrC57 BL/6-sham（8.05±1.06） vs C57 BL/6-AKI-CKD（25.35±3.02） vs C3^-/--sham（7.96±1.09） vs C3^-/--AKI-CKD（16.94±1.89）μmol/L, F=210.72, P＜0.01, BUN and urine protein levels in C57 BL/6-AKI-CKD group and C3^-/--AKI-CKD group increased, and the levels of renal complement C3, IL-1, IL-6 and TGF-β₁ increased, and the renal fibrosis was obvious. Compared with the C57 BL/6-AKI-CKD group, on Day 28, the levels of Scr, BUN and urinary protein in the C3^-/--AKI-CKD group were decreased, the levels of complement C3, IL-1, IL-6 and TGF-β₁ in the C3^-/--AKI-CKD group significantly declined, glomerular mesangial hyperplasia, glomerular sclerosis and kidney tubulointerstitial scores in the C3^-/--AKI-CKD group substantially decreased, the glomerular, renal tubule and renal interstitial collagen area in the C3^-/--AKI-CKD group decreased（all P＜0.05）. Conclusion Complement C3 participates in inflammation and post-injury fibrosis after IR-AKI.