OBJECTIVES: The aim of this study was to observe the impact of sirolimus on proteinuria in streptozotocin (STZ) induced diabetic rats. MATERIALS AND METHODS: weeks, respectively. Podocyte morphological changes were examined by electron microscopy and the ZO-1, podocin expressions in kidneys were detected by immunohistochemistry; the protein levels of Raptor and pS6 were measured by Western blot assay. RESULTS: <0.05). CONCLUSION: Sirolimus can reduce proteinuria and alleviate the early DN podocyte injury in diabetic rat model by inhibiting the activity of mTORC1; but in the advanced stage of DN, sirolimus can increase podocyte injury and urine protein level.