Aim: To study the correlation between neuroprotection effect of ginsenoside Rg1 and the activation of nuclear factor kappa B (NF-κB) in neuronal cells induced by β-amyloid peptide 25-35 (Aβ25-35). Methods: Rat astrocyte and hippocampal neuron cell models of Alzheimers disease (AD) were induced by Aβ25-35, respectively. The optimal concentration and duration of Aβ25-35 for cell models of AD and the optimal concentration and duration of Rg1 for pretreatment were determined according to cellular morphology and MTT colorimetric analysis. The activity of NF-κB in two kinds of cells was analyzed by laser scanning confocal microscope (LSCM) with double marked by FITC/PI. Results: Aβ 25-35 (40 μmol·L-1 for 24 h) was selected as the stable effective concentration and time point to make cell models of AD in neurons and astrocytes. 40 μmol·L-1 of Aβ 25-35 up-regulates the activity of NF-κB (P < 0.01) in astrocytes and downregulates the activity of NF-κB in neurons(P < 0.01). 2 μmol·L-1 of Ginsenoside Rg1 protects neurons through switching on the activation of NF-κB (P < 0.01), and protects astrocytes through inhibiting the degree of activation NF-κB (P < 0.01). Conclusion: Ginsenoside Rg1 protects neurons through down-regulating the activity of NF-κB in astrocytes and up-regulating the activity of NF-κB in neurons. These results give new evidence and mechanism that Ginsenoside Rg1 has therapeutic benefits in AD.