AIM: To study the effect of Sanhuang Gel on the expression of TLRs/NLRP3 signal pathway in auricle acne model rats, and to explore its mechanism in treating acne inflammatory injury. METHODS: A rat model of auricular acne was induced by applying 100% oleic acid to the opening of the right ear catheter and injecting Propionibacterium acnes. Rats were divided into normal group, model group, positive control group (clindamycin hydrochloride gel 10 mg/g) and Sanhuang Gel high, medium and low dose groups (280, 140 and 70 mg/g). Each drug group was given drug intervention for 28 days. The changes of auricle skin lesions in each group were observed; Hematoxylin-eosin (HE) staining was used to observe the pathological changes of auricle acne. The ultrastructural changes of auricle tissue cells were observed by transmission electron microscope (TEM). The distribution and expression changes of TLR2 and TLR4 in rat auricle tissue were detected by immunofluorescence. The expressions of TLR2, TLR4, NLRP3, ASC and Caspase-1 mRNA in rat auricle were detected by Real-time PCR. The expressions of TLR2, TLR4, NLRP3, ASC and Caspase-1 in rat auricle were detected by Western blot. RESULTS: Compared with the normal group, papules, pustules, inflammatory cell infiltration and obvious edema of mitochondria can be seen in the auricle tissue of the model group. The mRNA and protein expression levels of TLR2, TLR4, NLRP3, ASC andCaspase-1 increased significantly (P<0.01). Compared with the model group, the appearance and pathological damage of auricle in each treatment group were obviously alleviated, and the morphology and structure of mitochondria returned to normal. The mRNA expression levels of TLR2, TLR4, NLRP3, ASC and Caspase-1 decreased significantly (P<0.01). The expression levels of TLR2, TLR4,NLRP3, ASC and Caspase-1 in positive control group and high and middle dose groups decreased (P<0.01, P<0.05). The expression levels of ASC and Caspase-1 protein in low dose group were significantly decreased (P<0.01), but there was no significant difference in the expression levels of TLR2, TLR4 and NLRP3 protein (P>0.05). CONCLUSION: Sanhuang Gel can improve the pathological damage of auricle tissue and reduce immune inflammatory reaction in acne rats, and its mechanism may be related to regulating TLRs/NLRP3 signaling pathway.