Abstract: OBJECTIVE To investigate the antiangiogenesis effect and dose-effect relationship of indirubin(Ind) and its derivatives using zebrafish model which will contribute to the structure-activity relationship of new drugs. METHODS Intersegmental vessel number(ISV) in transgenic line VEGFR2: GFP zebrafish was used to evaluate angiogenesis inhibition effect after indirubin(Ind), its derivatives indirubin-3'-monoxime(IMO) and (2'Z,3'E)-6-Bromoindirubin-3'-oxime(BIO) treated zebrafish embryos. RESULTS At the same dose, BIO showed the strongest effect of antiangiogenesis, followed by IMO and Ind. The inhibition effects of three compounds were obviously dose-dependent. Furthermore, the median effective concentration(EC₅₀) of Ind, IMO and BIO were 89.10, 5.188 and 2.686 μmol·L^-1, respectively. CONCLUSION After addition of oximido at the C-3' and bromine at the C-6 in the structure of Ind, the solubility of IMO and BIO obviously increased and their antiangiogenesis effect enhanced simultaneously.