When the skin is injured, the subcutaneous tissues and organs are threatened by pathogens and excessive water loss. Wound dressings are, therefore, needed to protect the wound site from infection and improve the wound closure. Natural polysaccharides have been applied for various biomaterials including wound dressings, which show their advantages in biocompatibility, low toxicity, and pharmaceutical biomedical activity. In this study, a natural polysaccharide Bletilla striata polysaccharide (BSP) hydrogel is prepared by an oxidation and crosslinking methods. This BSP hydrogel represents preferable swelling ability and appropriate water vapor transmission rate. Using a full-thickness trauma mouse model, the hydrogel is applied on the in vivo cutaneous wound healing. Compared with the control groups, the BSP hydrogel achieves the much better healing results. The quantification of the infiltrating inflammatory cells and the level of tumor necrosis factor alpha (TNF-alpha) in the BSP group are attenuated, whereas the secretion of the epidermal growth factor (EGF) is highly elevated. On the 11th day after surgery, the wound area in the BSP hydrogel group is only 1/5-1/3 of those in the control groups. This new BSP hydrogel is proved to control the inflammatory responses and accelerate the wound closure and has potential application in wound healing. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.