Objective By comparing the changes in cerebral blood flow, neuronal morphology in brain tissue, and the levels of serum oxidation and inflammatory factors in models of cerebral hypoperfusion, three experimental rat models were assessed for their suitability as subjects of studies on the mechanisms and therapeutic drugs of cerebrovascular diseases and neurodegenerative diseases. Methods A total of 88 male SD rats were randomly divided into a sham operation group (n=16), classic bilateral common carotid artery occlusion group (classic 2-VO group, n=24), modified 2-VO group (n=24), and intraluminal thread technique group (n=24). Bilateral common carotid artery ligation was performed on the classic 2-VO group, while blood was drawn from the common carotid artery before ligation in the modified 2-VO group (1 mL/100 g). Middle cerebral artery occlusion was performed on the intraluminal thread technique group. In the sham operation groups of the first two models, the common carotid artery was separated but not ligated, while the proximal end of the common carotid artery and the external carotid artery were ligated; in addition, the bolt thread was not inserted in the sham group of the intraluminal thread technique group. Cerebral blood flow, infarct volume, serum inflammatory factor levels, hematoxylin and eosin-stained morphology, and ultrastructure of the hippocampal tissue were assessed at 1, 3, and 7 days after the operations. Results Laser speckle interferometry showed a decrease in cerebral blood flow of the modified 2-VO group that was more obvious than that of the other two groups. On day 7, only the modified 2-VO group still had significant differences in cerebral blood flow compared with the sham group, and it remained in a state of hypoperfusion (cerebral blood flow decreased by 30% compared with that before the operation). TTC staining showed that infarcts in the striata of the three groups gradually increased with time after the operation; 4 rats (about 26.7%) in the modified 2-VO group and 10 rats (about 66.7%) in the intraluminal thread technique group had infarcts in both the cortex and striatum. ELISA showed that the levels of inflammatory factors, such as TNF-α, IL-1β, and hs-CRP, in the three groups were increased after the operations, and levels of the pro-oxidation factor ROS were also increased. In contrast, levels of the antioxidant factor SOD decreased. On postoperative day 7, there was no significant difference in the hs-CRP of the classic 2-VO and intraluminal thread technique groups compared with that of the sham group. However, the modified 2-VO group still exhibited significant differences in all the above indicators compared with the sham group. Hematoxylin and eosin staining showed that the modified 2-VO group had more severe damage to the hippocampal CA1 and CA3 regions compared with the other groups. Transmission electron microscopy demonstrated that the modified 2-VO group showed more severe damage to the mitochondrial and endoplasmic reticulum in the hippocampal region compared with the other groups. Conclusions A cerebral hypoperfusion model was successfully established. Compared with the classic 2-VO and intraluminal thread techniques, the modified 2-VO method can induce more complete cerebral hypoperfusion and more severe neural damage within the same time frame, resembling the pathological state of human cerebral hypoperfusion more closely.