Bosentan prevented the development of dermal fibrosis, at least partially, by increasing the expression of Fli1 protein in lesional dermal fibroblasts of bleomycin (BLM)-induced systemic sclerosis (SSc) murine model. Wild-type C57BL/6 mice were injected with BLM (200 μg) or PBS into the skin of the back for 3 weeks. In some mice, bosentan (BOS) was administered intraperitoneally for 4 weeks from 1 week before BLM treatment. (A) The thickness of the skin on the back was evaluated by hematoxylin and eosin staining. The graph represents fold change in the dermal thickness in comparison to PBS-treated mice without bosentan administration, which was arbitrarily set at 1. ( B ) The expression levels of Fli1 protein were determined by immunohistochemistry. The arrows represent Fli1-positive dermal fibroblasts. ( C ) Double immunofluorescence for Fli1 (red) and α-SMA (green). Blue signals of nuclei were detected with 4′,6-diamidino-2-phenylindole (DAPI). The bottom panels represent the overlay of the three above. *P <0.05 versus PBS-treated mice without bosentan. **P <0.05 versus BLM-treated mice without bosentan. AU, arbitrary unit.