Objective: To investigate the effect and mechanism of α-lipoic acid(ALA) on the formation of hypertrophic scar(HTS) in rabbit ears. Methods: Eighteen New Zealand white rabbits were randomly divided into normal group, model group and 4%ALA group. After 28 days of treatment, the changes of scar related indexes were evaluated by hematoxylin-eosin(HE) staining, Masson pine(Masson) staining and immunohistochemical staining, the changes of oxidative stress related indexes were evaluated, and the expression of antioxidant pathway related proteins was detected by Western blotting. Results: The color, texture and volume of scar in 4%ALA group were lighter and softer than those in model group. The results of HE, Masson staining and immunohistochemical staining showed that the number of fibrous cells and the degree of fibrosis in the 4%ALA group were less than those in the model group. In the 4%ALA group, the content of malondialdehyde(MDA) was lower than that of the model group(P<0.001), the content of hydroxyproline(Hyp) was lower than that of the model group(P<0.01), the level of glutathione(GSH) was higher than that of the model group(P<0.01), the activity of T-SOD was higher than that of the model group(P<0.001). Western blotting showed that the content of NRF2 and the expression level of downstream antioxidant proteins in the 4%ALA group were higher than those in the model group. Conclusion ALA up-regulates NRF2 signal pathway to reduce the level of oxidative stress in HTS and inhibit scar proliferation in rabbit ears.