“Objective: To investigate the mechanism of action of Tripterygium wilfordii polysaccharides (TWM) in improving nephrotic syndrome in rats. The method used tail vein injection of doxorubicin to replicate the nephrotic syndrome model in rats. The successfully modeled rats were randomly divided into a model group (distilled water), a prednisone group (10 mg/kg), and TWM high and low dose groups (10, 5 mg/kg), and a blank group (distilled water) without modeling was set up, with 9 rats in each group. Each group of rats was orally administered with the corresponding medication/distilled water once a day for 6 consecutive weeks. Observe the pathological morphology of rat kidney tissue; Detect 24-hour urinary protein (24-hour UTP) and serum biochemical indicators [albumin (ALB), blood urea nitrogen (BUN), creatinine (SCr), total cholesterol (CHOL), triglycerides (TG)] levels in rats; Detect the levels of oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA)] in rat kidney tissue; Detect the mRNA and protein expression levels related to the hypoxia inducible factor 1 alpha (HIF-1 alpha)/microRNA-155-5p (miR-155-5p)/nuclear factor E2 related factor 2 (Nrf2) signaling pathway in rat kidney tissue. Compared with the blank group, the renal tissue structure of the model group rats was disordered, with a small amount of glomerular necrosis and edema of renal tubular epithelial cells; 24 h-UTP， The levels of SCr, BUN, CHOL, and TG in serum, MDA levels in renal tissue, HIF-1 α, Kelch like ECH related protein 1 (Keap1) mRNA and protein expression levels, and miR-155-5p expression levels in renal tissue were significantly increased (P<0.05); The levels of ALB in serum, SOD in renal tissue, and Nrf2 mRNA and protein expression were significantly reduced (P<0.05). Compared with the model group, the high-dose and low-dose TWM groups significantly improved renal injury in rats, and the levels of the above quantitative indicators were significantly reversed (P<0.05). Conclusion: TWM can alleviate oxidative stress damage and improve nephrotic syndrome in rats by regulating the HIF-1 α/miR-155-5p/Nrf2 signaling pathway”