Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta(25–35) in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta(25–35) for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta(25–35), and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta(25–35), and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta(25–35) via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling. Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta (25-35) in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta (25-35) for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta (25-35), and this effect was blocked by API-2 and PD98059. , ginsenoside Rb1 reversed reduced in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 horizontal induced by amyloid beta (25-35), and API-2 neutralized the effect of ginsenoside Rb1. The present results that that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta (25-35) via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling.