Vascular endothelial growth factor (VEGF) is a key regulator of blood vessel endothelium. Tissue levels of this angiogenesis marker are unknown in human gingival tissue, as is the correlation between vascular growth factors and hypoxia-inducible factor. We examined the expression of VEGF, type III tyrosine kinase receptors (VEGF-R2), platelet-endothelial cell adhesion molecule (CD31) and hypoxia-inducible factor (HIF) mRNA from human gingival tissue of the oral cavity. Tissue samples were from a small quantity of gingival sample biopsy with gingival sulcular depth (GSD) < 2 mm (Group 1), 2 to 4 mm (Group 2), and > 4 mm (Group 3). We found that the levels of VEGF-R2, CD31 and HIF mRNA were higher in the gingival tissue of Group 2 than that of Group 1, and VEGF in the Group 3 was also higher than that of Group 1. The different mRNA levels of these markers may reflect the mRNA levels reflect the vasculature state of gingival tissue based on GSD. VEGF-R2 and HIF also indicate the presence of an elongated blood vessel in the gingival tissue. In the early stage of angiogenesis, VEGF-R2 leads to expression of VEGF, and HIF-1 mediates increased VEGF expression in response to hypoxia in swollen tissues or during the expansion of periodontal tissues, which is useful in the early diagnosis of periodontal diseases.