Purpose This study aimed to examine the effects of swimming exercise pretreatment on a streptozotocin (STZ)-induced sporadic Alzheimer's disease (AD) rat model and provide an initial understanding of related molecular mechanisms. Methods Male 2.5-month-old Sprague–Dawley rats were divided into the following four groups: (a) control, (b) swim + vehicle, (c) STZ without swim, and (d) swim + STZ. The Barnes maze task and novel object recognition test were used to measure hippocampus-dependent spatial learning and working memory, respectively. Immunofluorescence staining, Western blot analysis, enzyme-linked immunosorbent assay (ELISA) analysis, and related assay kits were used to assess synaptic proteins, inflammatory cytokines, total antioxidant capacity, antioxidant enzymes, amyloid-beta production, and tau hyperphosphorylation. Results Behavioral tests revealed that exercise pretreatment could significantly inhibit STZ-induced cognitive dysfunction (P
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