Objective To investigate the change of Na+ /dicarboxylate cotransporter (SDCT) 1 expression in renal tissues of rats with nephrolithiasis induced by ethylene glycol (EG) and the mechanism of potassium citrate prevention. Methods Male Wistar rats were divided into control, nephrolithiasis and potassium citrate treated groups. Calcium oxalate crystal deposition and histological changes in kidney were examined by anatomical and light microscope. The plasma and urinary biochemical parameters, such as citrate, oxalate etc., were analyzed by routine biochemical method. The expression of SDCT1 mRNA in kidneys was determined by Northern blot, and the change of SDCT1 protein abundance was detected by immunohistochemistry. Results On day 3, the animals in the nephrolithiasis group had a higher level of SDCT1 mRNA and protein abundance in kidneys, as well as a lower level of citrate in the urine when compared with the control group. However none of the rats in this group had obviously calcium oxalate crystal deposition in kidneys. On day 7 and 14, the expression of SDCT1 mRNA and protein abundance were shown further increase, when the urinary citrate concentration was decreased progressively, and 87. 5% to 100% of the rats in this group displayed a large quantity of calcium crystal deposition in the kidney. In the potassium citrate treated group, both the expression of SDCT1 mRNA and protein abundance were shown almost complete inhibited during the whole experiment time, meanwhile the urinary citrate level was significantly elevated with time; furthermore, the occurrence of the renal crystal deposition decreased to 37. 5% on day 14, and the pathologic changes such as tubular dilation and inflammatory cells infiltration were shown to be alleviated. Conclusions The upregulation of SDCT1 mRNA and protein abundance in kidney has a close relationship with hypocitraturia, which may play an important role in the development of nephroliathisis. The treatment with potassium citrate has a beneficial effect on the experimental nephrolithiasis rats through inhibiting the expression of SDCT1 in the renal tissue.