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Background and purpose: A previous study (NCT01570231) showed that long-term remote ischemic preconditioning (RIPC) prevents cerebral ischemic events in patients with symptomatic intracranial atherosclerotic stenosis (SIAS). This study aims to further evaluate its beneficial impact on cerebral collateral flow and its underlying mechanisms.Methods: Patients with SIAS were randomized to RIPC group (n=30) or sham group (n=28, NCT01570231). RIPC was achieved by blocked bilateral arm arterial blood flow 5-min with double cuffs inflated to 200mmHg, followed by deflation for 5-min, and this was repeated 5 times automatically in every training cycle by the RIPC training device. Sham-RIPC was done in the same fashion with the exception of Inflating pressure at 60mmHg, which make the subjects feel a pressure but does not block the blood flow. RIPC and sham-RIPC were performed twice a day for 180 consecutive days. All subjects received standard background medical treatment. Status of cerebral collateral flow was evaluated with the regional leptomeningeal collateral (rLMC) score either by MRA and/or CTA. Plasma levels of VEGF were measured by ELISA, and circulating endothelial progenitor cells (EPCs) marked of CD45-CD133+CD34+VEGF-R2+ were quantified by flow cytometry from the mononuclear cells, which were isolated from venous blood samples at Day 0, Day 30 and 180.Results: 23(76.7%) patients in RIPC and 19(67.9%) in sham group completed MRA evaluation, and 7(23.5%) in RIPC and 9(32.1%) sham group finished CTA evaluation. The average rLMC score were 0.233±0.37, 1.133±0.24, and 2.066±0.31 in RIPC versus 0.214±0.35, 0.535±0.49 and 0.964±0.34 in sham group at Day0, 30 and 180(p0>0.05, p30<0.01, and p180<0.01). Plasma VEGF levels were 33.03±7.41, 136.88±60.79, and 285.37±77.75 in RIPC group versus 34.31±8.41, 66.85±16.89, and 93.86±18.97 in sham group (p0>0.05, p30<0.01, and p180<0.001). The ratios of EPCs were 0.018±0.012%, 0.086±0,015%, and 0.115±0.013% in RIPC group versus 0.019±0,011%, 0.045±0,012%, and 0.067±0,012% in sham group.Conclusions: Long-term regular RIPC appears to accelerate cerebral collateral open and vascular remodeling. It is associated with the elevated level of plasma VEGF and an increased ratio of circulating EPCs.