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Proteinuria is an important marker and is closely related to the progressive decline of renal function. Our previous research showed that angiopoietin-like-3 (ANGPTL3) plays a crucial role in proteinuria. In this study, we prepared an antibody against ANGPTL3 coil-coiled domain (ANGPTL3-CCD) and investigated the protective effect of anti -ANGPTL3-CCD antibody in mice with adriamycin-induced nephropathy. Nephropathy was established by adriamycin injection at a dose of 25 mg per kg in 8–12 week-old male mice in the ADR group. Blockade of ANGPTL3 by anti -ANGPTL3-CCD antibody (20 mg per kg) was performed every three days nine times after adriamycin injection in the ADR plus anti -angptl3-antibody group. The anti -ANGPTL3-CCD antibody can specifically recognize ANGPTL3. After anti -ANGPTL3-CCD antibody intervention, the urinary protein level in the ADR plus anti -angptl3-antibody group was significantly lower than that in the ADR group. Serum albumin was higher and triglyceride and total cholesterol were lower in the ADR plus anti -angptl3-antibody group than in the ADR group. The levels of serum creatinine did not significantly differ among the groups. Focal sclerotic glomeruli and podocyte foot processes extensive fusion were found in the renal tissue of the ADR group, whereas no sclerotic glomeruli and only partial fusion were found in the ADR plus anti -angptl3-antibody group. This study demonstrated that the anti -ANGPTL3-CCD antibody ameliorated proteinuria and podocyte dysfunction in adriamycin-induced nephropathy in mice. • ANGPTL3 is considered to be an important molecules involved in proteinuria. • Anti -ANGPTL3-CCD antibody decreased serum lipid levels. • Anti -ANGPTL3-CCD antibody ameliorated proteinuria and podocyte injury in adriamycin-induced nephropathy mice. [ABSTRACT FROM AUTHOR]