The objective of this study was to investigate the clinical effects of Tripterygium wilfordii on chronic glomerulo nephritis (CGN) and its mechanisms. Eighty-two cases of CGN treated in our hospital were randomly divided into observation and control groups. The control group was treated with conventional western medicine, and the observation group was treated with conventional western medicine and orally-administered T. wilfordii pills for three courses of treatment, each consisting of 4 weeks. Changes in serum reatinine, blood urea nitrogen, blood total cholesterol, blood albumin, and 24-h urine protein were observed. The levels of peripheral tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined with enzyme-linked immunosorbent assay. The curative effects of both groups were evaluated respectively. Both groups had significantly improved serum creatinine, blood urea nitrogen, blood total cholesterol, blood albumin, and 24-h urine protein (P < 0.05), and the observation group exhibited a more significant improvement (P < 0.05). TNF-α and IL-6 levels in both groups obviously decreased (P < 0.05), and the observation group exhibited remarkable changes (P < 0.05). After treatment, the total efficiency of the observation group was 90.24%, which was significantly higher than the 73.17% of the control group (P < 0.05). In conclusion, T. wilfordii can significantly improve kidney function and clinical symptoms in CGN patients, and the mechanism is possibly related to its inhibition of the secretion of TNF-α and IL-6.