The blood flow in the wound scar region is known to be decreased compared to the surrounding area of the wound closure. Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. It is suggested that HIF-1α signaling is involved in wound healing by regulating inflammatory cytokines such as such as TNF-α, MIP-1α, and MCP-1. Here, we investigated the role of HIF-1α signaling on M1/M2-like macrophage expression of heterozygous HIF-1α-deficient (HIF-1α HET) mice palatal wound healing. Histological examination showed that palatal wound closure in HIF-1α HET mice was delayed by the decreased infiltration of M1/M2 macrophage markers in parallel with the diminished production of Col1a1, MCP-1, MIP-1α compared with WT mice. These results suggest that HIF-1α signaling may play an important role in the regulation of palatal wound healing and HIF-1α deficiency aggravate the infiltration of M1/M2 macrophage.