AbstractAbdominal wall defect caused by open abdomen (OA) or abdominal trauma is a serious issue since it induces several clinical problems. Although a variety of prosthetic materials are commonly employed, complications occur including host soft tissue response, fistula formation and chronic patient discomfort. Recently, abundant natural polymers have been used for injectable hydrogel synthesis in tissue regeneration. In this study, we produced the chitosan - hyaluronic acid (CS/HA) hydrogel and investigated its effects on abdominal tissue regeneration. The physical and biological properties of the hydrogel were demonstrated to be suitable for application in abdominal wounds. In a rat model simulating open abdomen and large abdominal wall defect, rapid cellular response, sufficient ECM deposition and marked neovascularization were found after the application of the hydrogel, compared to the control group and fibrin gel group. Further, the possible mechanism of these findings was studied. Cytokines involved in angiogenesis and cellular response were increased and the skew toward M2 macrophages credited with the functions of anti-inflammation and tissue repair was showed in CS/HA hydrogel group. These findings suggested that CS/HA hydrogel could prevent the complications and was promising for abdominal tissue regeneration.