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Background and objectives Recently, there have been several attempts to apply the laser therapy to hypertrophic scars (HTS). In particular, the fractional laser is in the spotlight for its usefulness in rapid wound healing and dermal remodeling. However, most previous studies have focused on the ablative fractional laser (AFL), and there are no studies on the mechanism of the nonablative fractional laser (NAFL) effect in HTS treatment. In this study, we aimed to evaluate the changes in histology and molecular chemistry to provide scientific evidence for the early treatment of HTS with NAFL. Study design/materials and methods A total of 40 hypertrophic burn scars were made on the abdomens of two female pigs. After epithelialization, the HTS were randomly subdivided into four groups-control, AFL, NAFL (low energy), and NAFL (high energy). Laser treatment was initiated 1 week after the crust fell and the epithelium became covered, and it was repeated for six sessions over an interval of 2 weeks. Five excisional biopsies were obtained for histologic analysis and biomarker assessment. Results Histologically, dermal remodeling with thin coil-shaped collagen fibers was observed in the NAFL groups. It also showed a significant increase of matrix metalloproteinase-2 (MMP-2) and Decorin at 16 weeks in an enzyme-linked immunosorbent assay. The reverse-transcription polymerase chain reaction analysis showed a tendency that high-pulse energy of NAFL led to higher messenger RNA expression than did the low-energy group. Conclusion The NAFL-treated groups showed characteristic collagen re-arrangement and a significant increase in MMP-2 and Decorin. These molecular changes suggest that MMP-2 and Decorin play a significant role in dermal remodeling. Early NAFL treatment for HTS could be supported with both histological and molecular evidence. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.