Wound healing requires interplay between cells and molecules. Recent evidence has demonstrated that liquid bandages promote wound healing by forming a protective barrier against contamination, attenuating inflammation, and enhancing re-epithelialization and angiogenesis. In this study, we evaluated the wound healing activity of pyroxylin-based liquid bandage (LiQuiPlast®) in eight-week-old C57BL/6 male mice by generating a single 4 mm diameter full-thickness excisional skin wound on the dorsum. In the LiQuiPlast® group, the liquid bandage was applied on day 0 and was replaced every four days. Wound size was monitored every day for two weeks. The results showed that LiQuiPlast® was mechanically active (induced wound contraction), which promoted a significant wound size reduction (27 %−39 %, compared to the control group) on days 1–4 postinjury. In addition, a significant reduction in wound size was observed again in the LiQuiPlast® group (25 %−29 %, compared to the controls) on days 8−9 postinjury. LiQuiPlast®-treated wounds showed no scab. Immunohistochemistry analyses displayed a reduction in neutrophils and tumor necrosis factor-α levels in LiQuiPlast®-treated wounds, compared to the control group on day 4 postinjury (the inflammatory phase). In addition, LiQuiPlast®-treated mice had enhanced keratinocyte proliferation than control mice during this time. On day 13 postinjury, LiQuiPlast® significantly reduced hypertrophic scarring and enhanced expression and reorganization of collagen fiber compared to control mice. In conclusion, we show that LiQuiPlast® acts as a mechanically active protective film, which promotes moist wound healing by promoting wound contraction, no scab formation, attenuated inflammation, enhanced keratinocyte proliferation, and decreased scarring.