The process of skin wound healing involves the following three steps: inflammation, tissue formation, and tissue remodeling. These optimal steps are required for the development of normal wound healing. Many studies demonstrated that inflammasomes are involved in the innate immune response. In the present study, we examined whether the activation of inflammasomes affects the process of skin wound healing. The skin wound healing model was established using wild-type (WT), NACHT, LRR and PYD domains-containing protein 3 (NALP3) knockout (KO) and ASC-KO mice. The wounds were observed every other day and changes in wound size over time were measured using digital photography. Wound repair rate in NALP3-KO and ASC-KO mice was significantly inhibited compared with that in WT mice. Isoliquiritigenin, an inhibitor of NALP3, also decreased the rate of wound repair in WT mice. mRNA expression of pro-inflammatory cytokines in the wound sites of NALP3-KO mice was markedly decreased compared with WT mice. Treatment with adenosine triphosphate (ATP), a ligand of NALP3, up-regulated the mRNA expression of pro-inflammatory cytokines at the wound site and improved the rate of wound repair in the WT mice. Scratch assay in vitro study revealed that the administration with ATP accelerated wound closure in mouse embryonic fibroblasts from WT mice but not from NALP3-KO mice. The present study indicated that NALP3 pathway activation is involved in wound healing, and the topical use of ATP may be useful as an effective treatment for accelerating wound healing.