Progressive impairment of cognition is a key clinical feature of Alzheimer’s disease (AD), characterized by the accumulation of amyloid beta-protein (Aβ), tau hyperphosphorylation, neuroinflammation, and neuronal degeneration.Cannabidiol (CBD) is a safe, non-psychoactive phytocannabinoid that exhibits immunomodulatory activity in neurodegenerative disease, may ameliorate AD symptoms and slow cognitive decline.In this study, we aimed to examine whether chronic treatment with CBD can prevent cognitive and social deficits in a rat model of sporadic AD, and whether these changes are associated with alterations in AD neuropathology, neuroinflammation and cannabinoid receptor 1 (Cnr1) and 2 (Cnr2).Adult male rats received intracerebroventricular (ICV) injection of streptozotocin (STZ, 3mg/kg), a rat model of sporadic AD, followed by treatment with CBD (0.1 mg/kg, i.p.) for 2 weeks. After which, cognitive and social function were tested, as well as alterations in AD neuropathology, neuroinflammation and Cnr1/Cnr2 in the hippocampus.STZ rats showed impaired performance in object location and object recognition learning tasks and decreased social behavior. STZ affected AD neuropathology markers, i.e., increased Aβ and tau phosphorylation in the dentate gyrus (DG) region and mRNA levels of TREM2 and ApoE4. STZ increased neuroinflammatory markers, i.e., mRNA levels of TNF-alpha and NFkB1 in the CA1 area, as well as downregulated cnr1 and upregulated cnr2. Importantly, chronic treatment with CBD restored the STZ-induced behavioral deficits and molecular alterations.Our findings suggest that CBD is a promising drug in the treatment of inflammation-induced AD, able to prevent its onset. Further research is ongoing to understand the underlying mechanism.