Objective To investigate the effects of ginkgolide injection combined with clopidogrel on collateral circulation formation and HIF-VEGF-Notch pathway in rats with focal cerebral ischemia. Methods Totals of 60 SD rats were randomly divided into sham operation group， model group， ginkgolide injection group， clopidogrel group and ginkgolide injection + clopidogrel group. In addition to the shamoperated group， the middle cerebral artery occlusion method was used to establish the rat model of cerebral ischemia-reperfusion. After grouping and treating， Longa grading method was used to evaluate the neurological deficits of the rats in each group， cerebral infarction area was observed by triphenyl tetrazolium chloride （TTC） staining， microvessel density （CD31 positive cell expression） was detected by immunohistochemical staining， and expression of HIF-VEGF-Notch pathway-related protein in brain tissue was detected by real-time fluorescence quantitative （qRT-PCR） and Western blotting. Results Compared with the sham-operated group， the neurological deficit score， cerebral infarction area， CD31 positive cell expression， HIF-1α， VEGF， Notch1 mRNA expressions and protein expressions in the model group were increased （P ＜ 0.05）. Compared with the model group， the neurological deficit score and infarct area of rats in ginkgolide injection group， clopidogrel group， ginkgolide injection + clopidogrel group were decreased （P＜ 0.05）， while CD31 positive cell expression， HIF-1α， VEGF， Notch1 mRNA expressions and protein expressions in brain tissue were increased （P＜ 0.05）. Compared with ginkgolide injection group and clopidogrel group， the neurological deficit score and cerebral infarction area of rats in ginkgolide injection + clopidogrel group were decreased （P＜ 0.05）， and the CD31 positive cell expression， HIF-1α， VEGF， Notch1 mRNA expressions and protein expressions in brain tissue were increased （P ＜ 0.05）. Conclusions Ginkgolide injection and clopidogrel can promote collateral circulation formation and expression of HIF-VEGF-Notch pathway in rats with focal cerebral ischemia， and the combination of them has a synergistic effect.