During cerebrovascular development, an initial surplus of vessels is generated and subsequently refined through selective elimination to establish an efficient vascular network. Microglia are pivotal regulators of synaptic refinement and brain circuitry maturation, and despite their close interactions with cerebral vessels, whether and how they contribute to cerebrovascular pruning remains unclear. Here, to address this, we visualized and manipulated microglia-vessel interactions in the frontal cortex of postnatal day 11 mice. We found that microglia progressively approach cerebral vessels and subsequently mediate their pruning. Furthermore, we identify the PD-L1-PD-1 signaling axis as a regulator of microglia-mediated vascular pruning via microglial CD5L secretion. Altogether, our findings uncover a role for microglia in targeting redundant vasculature to facilitate vascular network formation during brain development.