Background: It is known that hydrogels based on carboxymethyl chitosan (CMCS) have properties controling microbial growth, reducing inflammatory cell infiltration, and promoting collagen deposition. Plantamajoside (PMS), a natural Chinese herbal medicine with biological activity, has the properties of reducing inflammation, anti-oxidation, and promoting wound healing. However, the effects of carboxymethyl chitosan/plantamajoside hydrogel on partial thickness burn wounds remain unclear. Methods: The healing effect of carboxymethyl chitosan/plantamajoside hydrogel was evaluated by in vitro cell viability assay, cell migration assay, and further evaluated in a rat model of partial-thickness burn wounds. Results: The hydrogels were highly porous with a pore size of about 250 mu m, and these pores were interconnected. After adding plantamajoside, a dense microstructure was further formed. The hydrogels containing 0.25% plantamajoside significantly increased the viability and migration of L929 cells (P < 0.05). Carboxymethyl chitosan/plantamajoside hydrogel significantly improved wound healing, granulation tissue proliferation and reepithelialization, and promoted collagen deposition (P < 0.05). Carboxymethyl chitosan/plantamajoside hydrogel also significantly decreased IL (interleukin)-1 beta, IL-6 and TNF-alpha expression, and increased IL-10 expression (P < 0.05). Furthermore, carboxymethyl chitosan/plantamajoside hydrogel significantly promoted the expression levels of VEGF, CD31, alpha-SMA (alpha-smooth muscle actin) and collagen III, and reduced the expression level of collagen I (P < 0.05). Our data suggest that carboxymethyl chitosan/plantamajoside hydrogel promotes burn wound healing by accelerating angiogenesis and collagen deposition and reducing the inflammatory response. (C) 2022 Published by Elsevier Ltd.