Angiogenesis plays central role in the formation of functional circulation system. Characterizations of the involved factors and signaling pathways remain to be the key interest in the angiogenesis research. In this report, we showed that c1qr/cd93 and c1qrl/clec14a are specifically expressed in the vascular endothelial cells during zebrafish development. Single mutation of c1qr or c1qrl is associated with slightly malformation of inter-segmental vessels (ISVs), whereas double mutant exhibits severe defects in the ISVs formation without affecting early vasculogenesis. Further studies reveal that the endothelial-endothelial junctional molecule Cdh5 becomes absent in the ISVs of the double mutant. Replenishment of Cdh5 efficiently rescue the impaired angiogenesis in the c1qr/c1qrl double mutant. These data demonstrate that c1qr and c1qrl redundantly regulate angiogenesis through controlling the expression of the endothelial junctional molecule Cdh5, thus playing an important role in angiogenesis.