Using a bleomycin-induced murine SSc model, we demonstrated for the first time that inhibiting miRNA-21a-5p improved fibrosis development by lowering signal transducer and activator of transcription 3 (STAT3) and increasing phosphatase and tensin homologue deleted on chromosome-10 (PTEN) in an in vivo system. Here, PTEN is linked to systemic sclerosis.