Blood-brain barrier (BBB) is an important structure of the neurovascular unit, and it can prevent the invasion of neurotoxic substances and pathogens through tight junctions and transporting proteins, maintaining the stability of the environment in the central nervous system. Compared with the BBB models in vitro, the ideal animal models can better simulate the physiological mechanism of BBB and play an important role in studying hemodynamics, barrier integrity, signal transduction, material exchange and so on. Reducing trauma and dynamic evaluation have become important needs in evaluating BBB models. The BBB model animals have changed from classical model animals (fruit flies and non-human primates) to transgenic and humanized animals (zebrafish and mice). With the development of new technology, BBB animal models with humanized protein expression and high-throughput screening are becoming the mainstream trend in this field.