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Anxiety, hippocampus synaptic plasticity deficit, as well as pro‐inflammatory cytokines, are involved in Alzheimer’s disease (AD). The present study is designed to evaluate the possible therapeutic effect of crocin on anxiety‐like behaviours, hippocampal synaptic plasticity and neuronal shape, as well as pro‐inflammatory cytokines in the hippocampus using in vivo amyloid‐beta (Aβ) models of AD. The Aβ peptide (1–42) was bilaterally injected into the frontal‐cortex. Five hours after the surgery, the rats were given intraperitoneal (IP) crocin (30 mg/kg) daily up to 12 days. Elevated plus maze results showed that crocin treatment after bilateral Aβ injection significantly increased the percentage of spent time into open arms, frequency of entries, and percentage of entries into open arms as compared with the Aβ group. In the open field test, the Aβ+crocin group showed a higher percentage of spent time in the centre and …