Aim To investigate the effect of Ginsenoside Rg1 on the improvement of nerve function in rats with Cerebral ischemia reperfusion and its mechanism. Methods Wistar rats with ischemia reperfusion injury were randomly divided into sham group, model group, edaravone group (3.2 mg/kg), low (10 mg), medium (20 mg) and high (50 mg) dose groups. At 1 d, 7 d and 14 d after administration, modified m-nss method was used to score neurological defects, and triphenyltetrazolium chloride (TTC) staining was used to determine the volume of cerebral infarction. TUNEL assay In situ was used to detect neuronal apoptosis in brain tissue. Immunohistochemistry was used to detect the levels of NF- kB and GAFP. The expression levels of FZD1, PIWIL1, FOXM1 mRNA and protein were detected by RT-PCR and Western Blot. Results Compared with model control group, the m-NSS were significantly decreased in low dose ginsenoside Rg1 group (P<0.05); the m-NSS were significantly decreased in medium and high dose groups (P<0.01); in low,medium and high dose ginsenoside Rg1 groups, the nerve apoptosis cells were significantly decreased (P<0.01), brain infarct volume were significantly reduced (P<0.01), the expression of NF-κB and GAFP were significantly decreased(P<0.01); The mRNA and protein expressions of FZD1, FOXM1 were significantly increased (P<0.01); The mRNA and protein expressions of PIWIL1 were significantly decreased (P<0.01). Conclusions Ginsenoside Rg1 can significantly improve the neural function of rats with Cerebral ischemia reperfusion. It may be achieved by regulating the expression of FZD1, PIWIL1, FOXM1 genes and proteins.