OBJECTIVE: Hypertrophic scars (HS) are a variety of skin tissue fibrosis disease that occurs in human skin, the effective therapeutic method of which is still inaccessible up to now. As a bioactive constituent of a well-known medical plant, (Danshen in Chinese), tanshinone II (TSA) is reported to inhibit cell proliferation in HS. Therefore, the aim of this study was to prepare TSA self-soluble microneedles to strengthen its dermal retention and break through the difficulty of significantly thickening epidermal connective tissue and stratum corneum at the HS site. The possible mechanism of action in suppressing HS was studied using human skin fibroblasts (HSF). METHODS: Tanshinone II self-dissolving microneedles (TSA-MN) was prepared using a negative mold casting method. The prescription process of microneedle was optimized by Box-Behnken effect surface method. Different media were selected to investigate the ability of transdermal absorption and release. Furthermore, according to Cell Counting Kit-8 (CCK8) method as well as the Western blot method, the effect of TSA-MN on the biological characteristics of HSF was investigated. RESULTS: With remarkable slow release effect and dermal retention, the release and transdermal properties of TSA-MN were better than both TSA and ordinary dosage forms. Its effect of HSF confirmed the essential decrease in cell motility during cell proliferation and cell migration , which plays a significant role in down-regulating the secretion of transforming growth factor- (TGF-) in HSF and increasing the expression level of Smad7. CONCLUSION: The prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars, with a stable dermal retention effect after process optimization.