MICAL-like 2 belongs to a multi-domain protein family and involves in a series of biological processes. However, the expression patterns and biological functions of this gene during embryonic development have not been well characterized. Here, the model organism zebrafish (Danio rerio) is utilized to examine the gene expression and its roles in vascular development. Whole-mount in situ hybridization analysis demonstrates that zebrafish micall2a is a maternal gene that commences to express at the zygote stage, and continues to larval stage. Moreover, micall2a is dynamically expressed in zebrafish developing vascular system during a time window encompassing many key steps in embryonic vasculogenesis and angiogenesis. Loss-of-function of micall2a in zebrafish embryos leads to deficiency in caudal vein plexus (CVP) formation, while the dorsal aorta (DA), posterior cardinal vein (PCV), and intersegmental vessels (ISVs) are not influenced. Our study suggests a role of MICALL2 in vascular development and offers a potential therapeutic target for vascular associated diseases.