Sericin and 4-hexylresorcinol (4HR) increased expression of vascular endothelial growth factor (VEGF) via different mechanisms. Sericin increased expression of hypoxia inducible factor-1α (HIF-1α) and HIF-2α. These transcription factors increase expression of VEGFs and tumor necrosis factor-α (TNF-α). Increased expression of matrix metalloproteinases (MMPs) is an indirect consequence. These cytokines promote macrophages to increase their anti-infection ability. 4HR directly increased expression of MMPs but decreased expression of TNF-α and reduced production of reactive oxygen species (ROS). An increase in expression of MMPs results in increased expression of VEGFs. Thus, these effects promote wound healing via increased angiogenesis and matrix remodeling. The difference between M1-like macrophages and M2-like macrophages is small, and regulation in the cytokine expression determines macrophage polarization. Thus, treatment with sericin or 4HR may allow for intentional polarization of macrophages.