BACKGROUND: Burn wound management is challenging, and while mesenchymal stem cell-derived exosomes show therapeutic potential, optimal delivery methods are unclear. AIM: To study chitosan (CS)-αβ-glycerophosphate (CS-αβ-GP) hydrogel crosslinked with adipose-derived stem cell exosomes (ASC-Exos) for healing deep burn injuries. METHODS: Rats with deep burn injuries were divided into the CS + ASCs-Exos group, the ASCs-Exos group, the CS group, and the control group. The healing rates on days 4, 7, and 14 after treatment were analyzed using ImageJ software. On day 14, the tissues were stained with hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemical analysis to evaluate tumor necrosis factor α, interleukin-6 (IL-6), IL-1α, IL-10, transforming growth factor β, and epidermal growth factor. The mRNA levels of IL-1α, CD86, C-C motif chemokine ligand 22, and CD163 were evaluated through quantitative polymerase chain reaction. RESULTS: The CS + ASC-Exos group exhibited enhanced healing, reduced lymphocyte infiltration, blood vessels, and muscle fiber distribution. Increased IL-10, transforming growth factor β, and epidermal growth factor and decreased tumor necrosis factor α, IL-1α, and IL-6 expression were observed. Quantitative polymerase chain reaction revealed reduced IL-1α and CD86 and increased C-C motif chemokine ligand 22 and CD163 expression. Protein analysis showed downregulation of phosphorylated inhibitor of kappa Balpha and P65 in the nuclear factor κB (NF-κB) pathway. ASC-Exos crosslinked with CS-αβ-GP hydrogel demonstrates superior effects in anti-inflammation, wound healing promotion, and promotion of M1 macrophage transformation to M2 macrophage by blocking the NF-κB pathway compared to ASC-Exos alone. CONCLUSION: Our research demonstrates that the ASC-Exos cross-linked CS-αβ-GP hydrogel represents an advanced therapeutic approach for treating deep burn wounds. It has anti-inflammatory effects, promotes wound healing, and facilitates the transition of M1 macrophages to M2 macrophages by blocking the NF-κB pathway.