Objective To investigate the effects of ginkgolide K on vascular endothelial growth factor （VEGF） expression and cerebral angiogenesis in mice with cerebral ischemia via the PI3K/Akt/mTOR signaling pathway. Methods A total of 40 C57BL/6 mice were randomly divided into five groups with 8 mice in each group： control group， MCAO group， GK-L group （3.5 mg/kg）， GK-M group （7 mg/kg） and GK-H group （14 mg/kg）, with 8 cases in each. MCAO rat models and oxygen glucose deprivation （OGD） in vitro models were established.The modified Neurological Severity Score （mNSS） was utilized to detect neurological deficits in mice. TTC staining was utilized to detect cerebral ischemic area of mice； immunofluorescence staining was utilized to detect cortical angiogenesis and astrocyte coverage in the peri-infarct cortex of ischemic mice. Hcmec / D3 cells were cultured and divided into control group， OGD group， OGD + CK group， OGD + LY group （LY as PI3K Signal pathway inhibitor） and OGD + GK + LY group. Endothelial cell activity was detected by CCK-8. Western blot was used to detected the protein expression of HIF-1α， VEGF and PI3K/Akt/mTOR pathwayrelated gene in endothelial cell； cell scratch test was used to detect the migration ability of endothelial cell； angiogenesis test was used to detect tube formation ability of endothelial cell. Results Compared with MCAO group ［（5.37±1.25）， （11.99±1.72）%］， the mNSS scores ［respectively （3.37±1.32）， （2.23±0.38）］and the area of cerebral ischemia ［（4.75±0.89）%， （2.42±0.42）%］of mice in GK-M group and GK-H group were significantly reduced （all P ＜ 0.05）. Compared with the number of EdU+/CD31+cells， the number of EdU +/ GFAP+cells and the astrocyte coverage of MCAO group ［（3.33±0.58）， （4.33±1.53）， （69.20±5.60）%］， GK Mouse EdU+/CD31+cell count ［（13.67±2.08），t=3.576］， EdU+/GFAP+cell count ［（8.33±1.53）， t=6.008］， and astrocyte coverage ［（82.26±7.77）%］increased significantly （P＜ 0.05）. Compared with the control group （100.31±3.01）%， the cell viability （52.37±9.06）% of the OGD group was significantly reduced （F=19.914， P＜ 0.05）， HIF-1α （0.17±0.02） and VEGF protein expression （0.18±0.03）， Akt and mTOR phosphorylation levels ［（0.28±0.06， 0.38±0.05）］ were significantly increased （P ＜ 0.05）； Compared with OGD group （0.28±0.06）， OGD+GK group cells HIF-1α （0.22±0.03） and VEGF protein expression （0.23±0.03）， Akt and mTOR phosphorylation levels ［（0.48±0.09），（0.52±0.05）］， cell viability ［（61.07±3.48）%］， mobility ［（85.26±11.03）%］ and the number of tubular structures ［（81.97±5.79）%］ were significantly increased （P ＜ 0.05）. The OGD+LY group showed the opposite change； PI3K signaling pathway inhibitor LY294002 could reverse the effect of GK on OGD cells. Conclusions Ginkgolide K up-regulates the expression of VEGF through PI3K/Akt/mTOR signaling pathway to promote cerebral angiogenesis and improve ischemic stroke in mice.