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BACKGROUND: Animal models of middle cerebral artery occlusion (MCAO) prepared by common carotid artery insertion or external carotid artery insertion are commonly used in preclinical studies of cerebral ischemia. However, there are few comparative studies on the difficulty of model preparation and microcirculatory perfusion during ischemic brain injury between the two methods of insertion. OBJECTIVE: To compare the MCAO models prepared by the common carotid artery insertion approach (CCAIA group) and external carotid artery insertion approach (ECAIA group) in the difficulty of model preparation and the differences in microcirculation perfusion. METHODS: Sprague-Dawley rats were randomly divided into sham-operated group, CCAIA group, and ECAIA group. Rats in the sham-operated group were anesthetized but without blood vessel ligation and suture insertion, and the other operations were the same as the above two methods. The modeling time, success rate of insertion, postoperative mortality and success rate of modeling were recorded. After the middle cerebral artery was blocked by suturing, laser speckle imaging technique was used to observe the changes of cerebral blood flow in the ischemic hemisphere and blood vessel diameter in the ischemic penumbra within 90 minutes after ischemia and ischemia-reperfusion. The neurological deficit score was evaluated by Longa’s method and modified neurological severity score at 2, 24, 48, and 72 hours postoperatively. TTC staining, dry-wet weight method, and Evans blue staining were used to calculate cerebral infarction rate, brain water content, and blood-brain barrier permeability at 72 hours postoperatively. Levels of endothelin-1, calcitonin gene-related peptide, cyclic adenosine monophosphate, prostaglandin E2, and nitric oxide in serum were determined by ELISA. RESULTS AND CONCLUSION: Compared with the ECAIA group, the CCAIA group had shorter operation time (P < 0.01) and higher success rate of modeling (P < 0.05). The cerebral blood flow, blood vessel diameter, and cyclic adenosine monophosphate level after reperfusion were significantly lower in the CCAIA group than the ECAIA group (P < 0.05). However, there was no significant difference between ECAIA and CCAIA groups in cerebral infarction rate, brain water content and blood-brain barrier permeability as well as in the serum levels of endothelin-1, calcitonin gene-related peptide, prostaglandin E2 and nitric oxide content (P > 0.05). To conclude, compared with the external carotid artery insertion, the common carotid artery insertion has the advantages of simple operation and high success rate of modeling, but results in an obvious microcirculation perfusion disorder in the cerebral cortex after reperfusion. Insufficient microcirculatory perfusion may be related to the decreased cyclic adenosine monophosphate level in serum. [ABSTRACT FROM AUTHOR]