ObjectiveTo observe the effect of tendon clearing combined with Zizhu ointment on the serum levels of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） inflammasomes， interleukin （IL）-1β， and IL-18 in the treatment of non-ischemic diabetic foot ulcers. MethodA total of 106 patients with non-defective diabetic foot ulcers who attended the outpatient clinic and wards of the Vascular Surgery Department of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from March 2023 to March 2024 were selected. The patients with non-ischemic diabetic foot ulcers who met the inclusion criteria were assigned with the random number table method into an observation group and a control group， with 53 patients in each group. Patients in both groups received basic treatment. The local ulcers in the observation group received tendon clearing combined with Zizhu ointment， while those in the control group received conventional debridement combined with topical solution of bovine basic fibroblast growth factor. The serum NLRP3， IL-1β， and IL-18 levels， ulcer area， traditional Chinese medicine （TCM） symptom scores， visual analogue scale （VAS） score， and DMIST score were measured and recorded in the two groups before and after treatment. The ulcer healing rate and incidence of adverse reactions were compared between the two groups. ResultThe observation group had higher ulcer healing rate than the control group （P<0.01）. After treatment， both groups showed lowered serum NLRP3， IL-1β， and IL-18 levels， reduced ulcer area， and declined TCM symptom score， VAS score， and DMIST score （P<0.01）. Moreover， these indicators were lower in the observation group than in the control group （P<0.05， P<0.01）. Neither group showed significant changes in the liver and kidney function indicators after treatment. Significant adverse reactions occurred in neither group during the treatment course. ConclusionTendon clearance combined with Zizhu ointment was effective and safe in treating non-ischemic diabetic foot ulcers. It may exert the therapeutic effect by reducing the inflammation of the local ulcers.