The present invention relates to a substantially pure biologically active consecutive anti-angiogenic polypeptide comprising the central region of human Histidine Rich Glycoprotein (HRGP). Said polypeptide is shown to comprise a potential endogenous, naturally occurring subfragment of human HRGP, comprising similar anti-angiogenic activities as the mature protein. The present invention also relates to one or more new biologically active subfragments of human HRGP, derived from said central region. Said subfragments are all characterized by having anti-angiogenic activity. One of the active subfragments is referred to as Pep2. Enscoped by the present invention are also anti-angiogenic subfragments derived from Pep2, one of them comprising a newly identified presently minimal functional entity.