This study aimed to investigate the impact of Wenyang Huoxue Lishui Formula (WHL) on the expression of Cathepsin L (CaL) in the renal podocytes of rats with doxorubicin-induced nephrosis (AIN). The AIN rats were treated with WHL for 4 week, and then 24 h urinary protein excretion (24- UP), serum total protein, and albumin were measured. Immunohistochemical method was used to observe the expression of CaL in the glomeruli, immunofluorescence staining was used to observe the expression of synaptopodin, and other renal pathological changes were observed simultaneously. WHL decreased 24-UP, increased both serum total protein and albumin, and decreased blood lipids (p<0.01). In addition, treatment with WHL downregulated CaL, upregulated synaptopodin, and improved the fusion of foot processes in the podocytes. WHL can down-regulate CaL and up-regulate synaptopodinin AIN rat models, thus helping to stabilize the actin skeleton, improve the fusion of podocytes, and reduce proteinuria.