Objective To study the changes of transcriptome levels in a Bama minipig model of hypertrophic scar during wound healing and pressure therapy by using RNA sequencing (RNA-seq) technique. Methods The Bama minipig model was established by skin wounds from the back and pressure (3.4 kPa) was initiated at 60 days after skin injury. Total RNA was extracted from scar tissues at 0, 14, 30, 60, and 90 days after skin injury and then sequenced. The resulting sequences were mapped to porcine reference genomes and transcriptomes were reconstructed to search for differentially expressed genes (DEGs). The DEGs were further subjected to GO and KEGG analysis using bioinformatics method, while part of the genes were selected for verification using qRT-PCR. Results After preprocessing, more than 78% reads in each group were accurately aligned to the reference sequence. The DEGs identification result showed that 568 genes were differentially expressed after pressure treatment, with 289 up-regulated and 279 down-regulated. GO enrichment analysis revealed that DEGs in each group were mainly associated with extracellular matrix, tissue development and skin development. KEGG analysis showed that the DEGs in each group during wound healing were mainly enriched in extracellular matrix-receptor interactions, focal adhesion and apoptosis pathways; while the DEGs after pressure treatment were mainly enriched in PI3K-Akt and MAPK signaling pathway except the pathways mentioned. qRT-PCR showed that the expression patterns of 6 DEGs were consistent with RNA-seq analysis, confirming the reliability of RNA-seq result. Conclusions RNA-Seq analysis identified differentially expressed genes in animal model of scars during wound healing and pressure therapy, which provided experimental evidence for clinical scar treatment.