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Background: Hypertrophic scar (HS) is a common disease in plastic and cosmetic surgery, with limited treatment options, and is a challenge for clinicians. Objectives: This study aimed to evaluate the efficacy of fractional carbon dioxide (CO2) laser combined with botulinum toxin type A (BTXA) in treating HSs in rabbit ears and to provide new strategies for treating HS. Methods: Twenty‐four New Zealand white rabbits with induced HSs were randomly divided into one control and three treatment groups. After 4 weeks of modeling, BTXA (2.0 U) was injected into the HS of the BTXA and combination groups, whereas a fractional CO2 laser (combo mode, deep energy: 12.5 mJ; super energy: 90 mJ) was used in the fractional CO2 laser and combination groups. The laser treatments were repeated after 2 weeks. The HSs in the rabbit ears were observed and photographed 5 weeks after the first treatment. The scar thickness in each group was measured and compared, and the scar elevation index (SEI) was determined using hematoxylin and eosin staining. Collagen content and alignment were observed using Masson's trichrome staining. Western blotting and immunohistochemistry were performed to analyze scar‐related protein levels. Results: Hypertrophic scars were reduced in all treatment groups compared with the control group. The combination group had lower scar thickness, SEI, and expression of scar‐related proteins in HSs, with an appearance similar to that of normal rabbit ear skin. Furthermore, the fibroblast content and collagen deposition decreased significantly in the combination group (p < 0.001). Conclusions: Fractional CO2 laser combined with BTXA more effectively reduced HSs by inhibiting fibroblast proliferation, decreasing transforming growth factor‐β1 and α‐ smooth muscle actin expression, and causing collagen remodeling. [ABSTRACT FROM AUTHOR]