Objective To investigate the neuroprotective effect of escitaloprarn on focal cerebral ischemia/ reperfilsion in rats and its possible mechanisms. Methods Seventy-five male Sprague-Dawley rats were randomly divided into three groups： sham operation, saline control and escitalopram intervention groups （n = 25 in each group）. A focal cerebral ischemia reperfusion model in rats was induced by the intraluminal suture method. The modified neurological severity scale was used to evaluate neurological deficit in rats （n = 5 in each group）. Laser confocal technology was used to observe the microvascular diameter, density, and total area in ischemic region （n = 5 in each group）. Enzyme-linked immunosorbent assay was used to detect the plasma concentration of vascular endothelial growth factor （VEGF） （n = 5 in each group）. [mmunohistochemical staining （n = 5 in each group） and Western blotting （n = 5 in each group） were used to detect the expression of VEGF in the ischemic brain tissue. Results At day 14 after modeling, the neurological deficit improved more significantly in the escitalopram intervention group than that in the saline control group （4. 39 ±0. 92 vs. 6. 57± 1.13; P =0. 015）. The 3D confocal vascular imaging showed that capillary diameter in the escitalopmm intervention group was significantly smaller than that in the saline control group （2. 93 ± 0. 19μm vs. 3.56 ± 0. 22 μm; P 〈 0. 01）; the vascular density was significantly higher than that in the saline control group （232. 68-± 12. 54/0. 002 mm3 vs. 176. 26 ± 10. 87/0. 002mm3; P =0. 000）; the total microvascular area was significantly greater than that in the saline control group （89 154± 3 298 μm2/0.002 mm3 vs. 75 368. 14± 3 519μm2/0. 002 mm3; P= 0. 000）. Enzyme-linked immunosorbent assay showed that the plasrtm VEGF concentration in the escitalopram intervention goup was significantly higher than that in the saline control group （50. 35 ± 5.44 pg/ml vs. 13.75 ± 4. 12 pg/ml; P = 0. 000）. Immunohistochemical analysis showed that the VEGF expression in ischemic brain tissue in the escitalopram intervention group was sigrhficantly higher than that in the saline control group （P = 0. 000）. Western blotting showed that the VEGF expression in ischemic brain tissue in the escitalopram intervention group was sigfificantly higher than that in the saline control group （0. 94 ±0. 18 vs. O. 62 ±0. 22; P =0. 006）. Conclusions Escitalopram may reduce neurological deficit in cerebral ischemia/reperfusion in rats. Its mechanisms may be associated with VEGF-mediated angiogenesis.