The glymphatic system is an important pathway responsible for clearing metabolic wastes (such as β-amyloid) in the cen-tral nervous system,regulates the exchange between cerebrospinal fluid (CSF) and interstitial fluid (ISF),and therefore is ofimportant significance for the maintenance of homeostasis of the central nervous system.Sleep deprivation causes cognitivedecline and increases the risk of neurodegenerative diseases.Ginsenoside Rb1 is a tetracyclic triterpenoid saponin extractedfrom ginseng root that can alleviate cognitive dysfunction induced by sleep deprivation.The present study was to investigatethe effect of sleep deprivation on glymphatic system and the role of ginsenoside Rb1 in the regulation of glymphatic systemdysfunction induced by sleep deprivation.Male C57 mice,aged 6-8 weeks,were randomly assigned to blank (no sleep depri-vation and ginsenoside Rb1 treatment),model (sleep deprivation and saline injection),control (no sleep deprivation butginsenoside Rb1 intervention) and treatment (sleep deprivation and ginsenoside Rb1 treatment) groups (n =10 per group).Rapid eye movement sleep deprivation was performed in the model and treatment groups using the multiple platformmethod.Ginsenoside Rb1 was intraperitoneally injected at 20 mg/kg body weight.The function of the glymphatic systemwas evaluated by two photon microscopy in vivo and immunostaining methods ex vivo.CSF tracers influx into the brainparenchyma of sleep-deprived mice reduced to about 60% compared with that in mice not subjected to sleep deprivation.After treatment with ginsenoside Rb1,CSF tracers influx into the brain parenchyma in the sleep-deprived mice increasedsignificantly (about 90%,P < 0.01) compared with no ginsenoside Rb1 treatment.In normal mice treated with GinsenosideRb1 alone,CSF-ISF exchange was not significantly increased,suggesting that the treatment effect of ginsenoside Rb1 is re-lated to glymphatic system function impairment.Our data demonstrate that ginsenoside Rb1 can effectively improve sleepdeprivation-caused impairment of the glymphatic system,suggesting that ginsenoside Rb 1 can be used for the treatment ofAlzheimers disease and other neurodegenerative diseases.