At present, seeking an effective dressing for wound regeneration has drawn considerable interest. In this paper, a novel agarose-grafting-hyaluronan (Ag-g-HA) scaffold was synthesized for rapid wound healing. Elemental analysis results showed that the HA grafting rate of Ag-g-HA was ∼69%. Ag-g-HA remained bioactive to accelerate cell proliferation and stimulate secretion of TNF-α for macrophagocyte RAW 264.7, and collagen I and collagen III for fibroblast 3T3. An i n vivo study demonstrated that Ag-g-HA showed a faster repair cycle and a better skin histological structure for a full-thickness skin defect. The collagen I, collagen III and TNF-α secreted by mice for Ag-g-HA were similiar to HA. Ag-g-HA showed a similiar biological activity to HA but had a longer degradation time through its improved insolubility. These findings demonstrate that the Ag-g-HA scaffold accelerated wound healing, and could be a promising novel scaffold for tissue engineering and regenerative medicine.