Objective: To study the nephrotoxicity of aristolochic acid in a zebrafish embryo model. Methods: Zebrafish embryos at 3 days post-fertilization stage were treated with aristolochic acid. Morphological changes of embryos and kidney were observed. Histological structure of kidney were further examined by tissue sections. The expression level of Nephrin was tested by qPCR to explore the podocyte function in embryo kidney treated with aristolochic acid. Results: Embryos treated with 20 μmol/L AA for 24h exhibited periocular edema and malformed kidney phenotypes. As the exposure dosages of AA increased, besides periocular edema, embryos also displayed impaired blood circulation, such as decreased heart rate and blood flow, and even blood stasis.Embryos treated with AA displayed cystic glomeruli and disorganized pronephric tubules. qPCR showed that AA treatment can significantly down-regulate the expression of nephrin in comparison with mock-control littermates(P<0.01). Conclusion: AA caused profound nephrotoxicity in histological structure and biological function of zebrafish embryos. Dysfunction of podocyte may involve in AA-induced renal impairment.