Abstract： Objective： To observe the efficacy of Niaoganning Granules combined with Piperacillin Sodium and Tazobactam Sodium in treating urinary tract infections after ureteroscopic lithotripsy and its effects on Toll-like receptor 4（ TLR4），soluble interleukin-2 receptor（ sIL-2R），and high mobility group box 1 protein（ HMGB1）. Methods：A total of 100 patients with urinary tract infections after ureteroscopic lithotripsy treated at Urological Surgery， Xianju People's Hospital from January 2022 to December 2023 were divided into the control group and the observation group using the random number table method（ 50 cases each）. The control group received Piperacillin Sodium and Tazobactam Sodium，while the observation group received additional Niaoganning Granules. Both groups were treated for seven days. Clinical efficacy and pathogen eradication rates were compared between the two groups. The traditional Chinese medicine syndrome scores， and levels of IL-6， MCP-1， sIL-2R， HMGB1， TLR4， and neutrophil gelatinase-associated lipocalin （NGAL） before and after treatment were compared between the two groups. Results：The total effective rate was 92.00%（ 46/50） in the observation group，higher than that of 76.00%（ 38/50） in the control group（ P＜0.05）. The pathogen eradication rate was 96.00% （48/50） in the observation group， higher than that of 82.00% （41/50） in the control group （P＜0.05）. After treatment， the scores of urethral pain， burning sensation， frequent urination， urgency， and dark red urine color in both groups decreased compared to before treatment （P＜0.05）， and the observation group had lower scores of urethral pain， burning sensation， frequent urination， urgency， and dark red urine color than the control group （P＜0.05）. After treatment， the levels of IL-6， MCP-1， NGAL， sIL-2R， and HMGB1 in both groups decreased compared to before treatment （P＜0.05），and the levels of IL-6，MCP-1，NGAL， sIL-2R，and HMGB1 in the observation group were lower than those in the control group （P＜0.05）. After treatment， the relative expression level of TLR4 in both groups decreased compared to before treatment （P＜0.05）， and the relative expression level of TLR4 in the observation group was lower than that in the control group （P＜0.05）. Conclusion： The therapy of Niaoganning Granules combined with Piperacillin Sodium and Tazobactam Sodium demonstrates superior efficacy in treating post-lithotripsy urinary tract infections by enhancing pathogen eradication rates and modulating inflammatory responses through down-regulating the TLR4/sIL-2R/HMGB1 pathways.