Objective Osteopontin (OPN) plays an important role in inhibiting the formation of urolithiasis. This inhibition mechanism of stone formation is still controversial. In this study, we want to know the expression of OPN and mRNA of kidneys of rats models nephrolithiasis which were treated by potassium citrate, forword Probe the relationship between Citrate and OPN(between Citrate and OPN mRNA). This will provide the experimental basis for study of the mechanism of renal stone formation, and will be helpful to the clinical prevention of nephrolithiasis.Methods We used 1% ethylene glycol and 1% ammonium chloride mixture of lithogenic agent-induced rat model of experimental stone. Thirty-two adult male wistar strain rats were randomly divided into four groups (n=8 each): normal control group、the citrate group、stone formation group (ethylene glycol (EG) and ammonium chloride)、the stone formation+citrate group. After 4 weeks, the rats were killed, kedney was used for histological examination(HE).The formation of renal stone and the expression of OPN and OPN mRNA in rat renal tissue of each group were examed with HE staining, Immunohistochemistry methods and RT-PCR. The content of calcic and oxalic acid of 24 hour’s urine were exzamine with EDTA method and colorimetric method.Results①Histological examination Crystal formation:The formation of renal stone in the stone formation+citrate group was lower than in the stone group(P<0.05). The control groupand the citrate group have no renal stone formation;②The content of calcic and oxalic acid of 24 hour’s urine: The content of calcic and oxalic acid of 24 hour’s urine in the stone formation+citrate group was lower than in the stone group(P<0.05). But They all were highter than the control group and the citrate group;③Immunohistochemistry: The expression of OPN in the stone formation citrate group is less than the stone group remarkablely(P<0.05). Yet that in the contol group and in cirate group is the same, but very weak.④RT-PCR Every group has the different expression of OPN mRNA in renal tissue. The mRNA expression level of OPN in renal tissues in the stone formation+citrate group and stone group than the contol group and citrate group. But the mRNA expression level of OPN of the stone group was more than the stone formation+citrate group(P<0.05).Concluion Citrate can reduce crystal formation and decrease the deposit of calcium oxalate in renal tissue and the crystal damaging on renal duct. The citrate can inhibit the OPN expression and OPN mRNA expression so as to block the format ion of renal calcium oxalate stone in rats potently.