Objective To observe the changes of renal tubules injury and interstitial fibrosis level in the C57BL/6 mouse models of chronic kidney disease (CKD), and provide animal experimental evidence for study the acute kidney injury (AKI) to chronic kidney disease progression as well as the mechanisms of this progression. Methods 24 male C57BL/6 mice (8-week aged) were randomly and averagely divided into control group, low-dose cisplatin group, medium-dose cisplatin group, and high-dose cisplatin group. Mice in cisplatin group were administrated with 5mg/kg or 7mg/kg or 10 mg/kg cisplatin by intraperitoneal injection once a week for 4 weeks. Then the mice were sacrificed, and plasma and kidney samples were collected for subsequent tests. Plasma creatinine and 24-hour proteinuria were detected to assess renal function. Pathological changes were observed by Periodic acid–Schiff (PAS) staining. To evaluate renal tubules injury, the expression of kidney injury molecule 1(KIM-1) were examined by immunohistochemistry and the level of urinary N-Acetyl-β-D-glucosaminidase were detected by commercial kit. In addition, the infiltration of CD3-positive T cells and F4/80-positive macrophages was explored by immunohistochemistry (IHC) and immunofluorescence. Finally, to assess renal fibrosis, the expression of collagen I and α-smooth muscle actin (α-SMA) were tested by immunohistochemistry, while total kidney collagen was detected by PicroSirius Red staining. Results In contrast to the normal control group, the kidney injury became more serious in mice with cisplatin treatment as cisplatin concentration increased. Particularly, the significant kidney damage was observed in high-dose cisplatin group. When compared with control group, renal function in high-dose cisplatin group was significantly impaired evidencing by a increase in plasma creatinine and 24-hour urinary protein (P＜0.05 and P＜0.001) . Morphologically, numerous clear vacuoles and necrosis are present in renal tubule epithelial cells in high-dose cisplatin group mice, meanwhile, the expression of KIM-1 was markedly up-regulated and the level of urinary NAG was elevated. Additionally, the infiltration of CD3-positive T cells and F4/80-positive macrophages was enhanced in mice with high-dose cisplatin injection when compared with control group. Furthermore, data from immunohistochemistry and PicroSirius Red staining have shown that in contrast to normal mice, mice administrated by high-dose cisplatin developed renal fibrosis evidenced by markedly up-regulated expression of collagen I and α-SMA. Conclusions Repeated administration of 4-week 10mg/kg cisplatin can induced mice chronic renal insufficiency, which as a novel model applies the research about mechanism underlying AKI to CKD.