"The extract of shikon" (SK) and shikonin play important roles in the devel
opment of granulomatous tissue formation. To reveal the augmenting effect o
f SK or shikonin on vascular endothelial growth factor (VEGF) production an
d neovascularization, we investigated murine granulomatous tissue induced b
y SK and shikonin, comparing them to pouches in which trehalose 6,6 ' -dimy
colate (TDM) was injected, The development of granulomatous tissue formatio
n was evaluated by the wet weight of pouch walls, At day 5 and 7 after SK a
nd shikonin injection, prominent granulomatous tissue formation was detecte
d. Histological observations on the development of granulomatous tissue sho
wed that the pouch was formed in the submuscular connective tissue and necr
otic tissue directly facing the cavity and granulomatous tissue developed i
n the connective tissue. At day 1, VEGF-positive neutrophils accumulated in
the pouch wall. Granulomatous tissue formation and neovascularization by i
njection of SK or shikonin was not more prominent than TDM, However, the pr
esent results indicate that SK and shikonin induce neovascularization in gr
anulomatous tissue.