〔Abstract〕 Objective To study the mechanism of Jiawei Qihuang Yin in improving diabetic nephropathy (DN) through PTEN/ phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway. Methods Sprague Dawle (SD) rats were fed with high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to establish a DN model. The rats were divided by completely random method into model group, low-dose group, middle-dose group, high-dose group of Jiawei Qihuang Yin and losartan group. There were 10 rats in each group. According to the conversion of clinical dosage, the low-dose group, middle-dose group and high-dose group of Jiawei Qihuang Yin were set (crude drug content: 200, 400, 800 mg·kg^-1 ·d^-1. And the blank group and model group were given 0.9% sodium chloride injection by gavage. After 8 weeks, the levels of 24-hour urine protein, serum creatinine (SCr), and blood urea nitrogen (BUN) were measured. The pathological changes of kidney were observed by Hematoxylin-eosin (HE) staining, and the protein expressions of PTEN, PI3K, Akt and mTOR in renal tissue were detected by immunohistochemistry. Results Compared with the blank group, the levels of 24 h urine protein, SCr and BUN in the model group were significantly increased (P < 0.0001), and the renal function indexes in the model group were lower than those in the model group after intervention with Jiawei Qihuang Yin (P < 0.001). Immunohistochemical results showed that the expression of PTEN in the model group decreased, while the expression of PI3K, Akt, and mTOR increased (P<0.01). After the intervention of Jiawei Qihuang Yin, the expression of PTEN was increased, while the expression of PI3K, Akt and mTOR decreased, with statistical significances (P < 0.05). There was no significant difference between the high-dose group of Jiawei Qihuang Drink and the losartan group (P > 0.05). Conclusion Jiawei Qihuang Yin may delay the development of DN through the PTEN/PI3K/Akt/mTOR pathway.