Abstract: Objective:To explore the protective effects of Gracilaria lemaneiformis polysaccharides(GPs)on D-galactose(D-gal)and aluminumchloride(AlCl₃) induced neurotoxicity in rats. Methods:Alzheimer’s disease(AD) rats was established by injecting both D-gal and AlCl₃ into abdominal cavity for 42 d. Rats were divided into control group,AD group,AD+GPs(300 mg/kg,p.o.)group and AD+GPs(600 mg/kg,p.o.)group. Behavioral responses of animals were assessed in a Morris water maze(MWM). Oxidative stress parameters and histopathological studies were carried out in hippocampus. Results:Oral administration of GPs significantly decreased mean escape latency time as compared to the AD group on the second,third,fourth day of the acquisition trial(low-dose GPs group vs. the AD group:P<0.05,0.05 and 0.01,respectively;high-dose GPs group vs. the AD group:P<0.01,0.01 and 0.01,respectively). In the spatial exploration test,rats treated with GPs got higher numbers of platform crossings than that in the AD group(P<0.01). Compared with the AD group,both low-dose and high-dose GPs treatments could well maintain the ordered arrangement of pyramidal neurons. The reduction of the hippocampus superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)activities were ameliorated by oral administration of GPs(all P<0.01).Furthermore,oral administration of GPs significantly prevented D-gal and AlCl₃-induced rise in malondialdehyde(MDA)level(all P<0.01). Conclusion:GPs could protect cognitive impairments and morphological alterations caused by D-gal and AlCl₃ toxicity in rats. The neuroprotective effect of GPs might be mediated through its antioxidant and free radical scavenging effects.