Abstract: To investigate the locations of sodium retention and the mechanism of its occurrence in the rat model of adriamycin nephrotic syndrome. Methods: The nephrotic syndrome model was established by tail vein injections of adriamycin twice two weeks(4 mg/kg in first week and 2 mg/kg in second week). Urine and blood biochemical parameters were detected; the contents of water and sodium in rat skin were detected respectively by desiccation and atomic absorption spectrometry; the content of glycosaminoglycan was analyzed by ELISA; the expression of tonicity-responsive enhancer binding protein(TonEBP), vascular endothelial growth factor C(VEGFC), vascular endothelial growth factor receptor 3(VEGFR3) and lymphatic vessel hyaluronan receptor-1(LYVE-1) in the renal cortical was detected by Western blot; the lymphatic vessels distribution in the renal cortex was measured by immunofluorescence. Results: the model rats had increased urinary protein excretion, and abnormal renal function and lipid, which suggested the model was successfully established. The excretion of Na+in urine decreased, the content of skin sodium and glycosaminoglycan in skin obviously increased, the expression of TonEBP, VEGFC, VEGFR3, LYVE-1 in renal cortical markedly increased, and density of lymphatic vessels in renal cortical notably increased(P<0.05 orP<0.01). Conclusion Sodium retained in nephrotic syndrome rats may be stored in the skin, which is related to the TonEBP/VEGFC/VEGFR3 pathway.