Abstract： Objective To investigate the effect of magnesium sulfate on prevention and treatment of renal interstitial fibrosis and its mechanism. Methods The unilateral ureteral obstruction(UUO)model was used,and the SD rats were randomly divided into the sham operation group(group A),model group(group B),low dose magnesium sulfate group(group C)and high dose magnesium sulfate group(group D). The sham operation group and the model group were given equal volume of normal saline by intraperitoneal injection daily. The low dose magnesium sulfate group and high dose magnesium sulfate group were given 100 mg·kg-1·d-1 and 300 mg·kg-1·d-1 magnesium sulfate by intraperitoneal injection,respectively. The levels of TGF - β1, Nox4, p - ERK1/2 and type Ⅲ collagen in the kidney tissues were measured by immunohistochemistry and Western blot. Results The immunohistochemistry findings showed that:the positive expression of TGF-β1,Nox4,p-ERK1/2 and type Ⅲ collagen in the renal tubular epithelial cells of SD rats in group A was low;In group B. the renal tubular epithelial cells was significantly increased long with the progression of the disease,and there was statistically significant difference compared with that in group A&nbsp;(P<0.05);In groups C and D,the positive expression of the four indicators was significantly decreased compared with that in group B (P<0.05),but still higher than that in group A (P<0.05). The positive expression level in group D was significantly decreased compared with that group C(P<0.05). The findings of Western blot of Nox4 were similar to those of immunohistochemistry. Short-term observation of magnesium sulfate treatment effect was dependent on time and dose. Conclusion Magnesium sulfate shows the effect of protecting renal interstitial fibrosis,and its mechanism may be related to reducing the expression of TGF-β1, p-ERK1/2 and type Ⅲ collagen in the kidney by down-regulating the expression of Nox4.