This study assessed the effects of probiotic supplementation on spatial learning and memory, long-term potentiation (LTP), paired-pulse facilitation (PPF) ratios, nitric oxide (NO) concentrations, and lipid profiles in a rat model of amyloid beta (Aβ)(1-42)-induced Alzheimer’s disease (AD). Forty rats were randomly divided into 4 groups. The sham (control and prevention) group received intracerebroventricular (ICV) injections of artificial cerebrospinal fluid, the Alzheimer group received ICV injection of Aβ(1-42), and the probiotic+Alzheimer group received 500 mg probiotics daily (15 ×10<SUP>9</SUP> colony-forming unit) by gavage for 4 weeks before and 2 weeks after injection of Aβ(1-42). The Morris water maze test was performed for evaluation of spatial learning and memory. LTP and PPF ratios were measured to evaluate longterm synaptic plasticity and pre-synaptic mechanisms, respectively. The results showed that probiotic supplementation significantly improved learning, but not memory impairment, and increased PPF ratios compared to those in the Alzheimer group. Both Aβ(1-42) injection and probiotic supplementation alone did not significantly effect plasma level of NO. Probiotic supplementation of rats in the probiotic (6 weeks)+Alzheimer group decreased serum levels of total cholesterol, triglyceride, and very low-density lipoprotein-cholesterol significantly compared to the Alzheimer group. The results of this study suggest that probiotic supplementation may positively impact learning capacity and LTP in rats with AD, most likely via the release of neurotransmitters via presynaptic mechanisms or via a protective effect on serum lipid profiles.