Objective: To elucidate how hemorrhoidal analgesic cream (HAC), grounded in the traditional Chinese medicine (TCM) “elevation and causation” theory, promotes postoperative wound healing after anal fistula surgery in diabetic rats by modulating the Keap1/Nrf2/ARE pathway. Methods: The DM rat model was induced by high glucose and high fat feed combined with streptozotocin (STZ) to construct the postoperative trauma of anal fistula. The rats were divided into a blank control group, model group, sham-operated group, experimental group (HAC treatment), and positive control group (recombinant human epidermal growth factor gel). HAC’s impact on wound healing was evaluated by measuring fasting blood glucose (FPG), glycated hemoglobin (HbA1c), serum inflammatory factors (TNF-α, IL-6), oxidative stress markers (MDA, SOD), and Nrf2 pathway proteins and mRNA. Results: The HAC group showed a significantly higher wound healing rate (92.85 ± 3.41%, P < 0.01), reduced FPG and HbA1c levels (P < 0.05), reduced TNF-α, IL-6, and MDA levels (P < 0.01), increased SOD activity (P < 0.05), and activation of the Keap1/Nrf2/ARE pathway.Conclusion: HAC reduces oxidative stress and inflammation by regulating the Keap1/Nrf2/ARE pathway, which validates its scientific value in promoting wound healing after DM fistula surgery.