Abstract： Objective： To discuss the effect of Yiqi Gushen prescription on kidney function and miR- 192 in rats with diabetic nephropathy(DN) induced by streptozotocin(STZ)，and its preventive and therapeutic effect and mechanism on DN. Methods： A total of 36 cases of SD rats were randomly divided into the normal group， the model group， the irbesartan group， and the groups of Yiqi Gushen prescription in low， middle and high dose(the low- dose group， the middle- dose group and the high-dose group)，6 rats in each group. Except the normal group，the rat models with DN were replicated. The groups of Yiqi Gushen prescription in low，middle and high dose were given water decoction of Yiqi Gushen prescription in 0.047 g/kg，0.141 g/kg and 0.282 g/kg respectively. The irbesartan group was given irbesartan in 20 mg/kg. The model group and the normal group were administered with the equivalent volume of saline by gavage，once a day，for six weeks. The intragastric administration， drinking amount and urine volume of rats in each group were detected； automatic biochemical analyzer was used to detect alanine aminatransferase(ALT)，aspartate aminotransferase(AST)，blood urea nitrogen(BUN) and serum creatinine(SCr) ； RT-PCR method was used to quantitatively detect the expression of miR-192 mRNA. Results ： Compared with those in the normal group，in the model group，the amount of food intake，drinking amount，urine volume， the contents of ALT，AST，BUN and SCr in serum，as well as the expression of miR-192 mRNA of rats were all increased (P＜0.05). Compared with those in the model group， in the irbesartan group， the middle- dose group and the high- dose group，the drinking amount and urine volume of rats were decreased(P＜0.05)，and urine volume in the low-dose group was decreased(P＜0.05)；in the irbesartan group and the high-dose group，the contents of ALT，AST，BUN and SCr in serum were decreased(P＜0.05)，and the above contents in the low-dose group and the middle-dose group were decreased，(P＜ 0.05)，but there was significant difference only being found in the comparison of ALT(P＜0.05)；in the irbesartan group and the groups of Yiqi Gushen prescription in each dose，the expression of miR-192 mRNA was decreased(P＜0.05). Compared with those in the irbesartan group，in the low- dose group and the middle- dose group，the contents of ALT，AST and SCr in serum were higher(P＜0.05)；the expression of miR-192 mRNA in the high-dose group was decreased(P＜0.05). Conclusion： Yiqi Gushen prescription can effectively treat DN， whose mechanism may be related to the inhibition of the expression of miR-192 in the kidney of rats with DN.