Background: Crocus sativus L., (Iridaceace), known as saffron, is used in traditional medicine for different purposes such as memory improvment. Crocin is one of the pharmacologically active constituents responsible for many medicinal properties of saffron. Objectives: In this study, the effects of crocin, an active saffron constituent, on hyoscine induced memory impairment and its effect on protein and mRNA transcript levels of CREB (cAMP response element binding protein), BDNF (brain-derived neurotrophic factor), and phospho-CREB (p-CREB) were investigated in rat hippocampus. Methods: Rats were intraperitoneally treated with crocin (10, 20, and 40 mg/kg), normal saline (1 mL/kg), and rivastigmine (1.5 mg/kg) 30 minutes prior to hyoscine (1 mg/kg) for five days. The effects were studied on spacial learning and memory using Morris water maze. Protein and transcript levels of CREB and BDNF were analyzed using western blotting and qRT PCR methods, respectively. Results: Five days treatment with crocin (20 and 40 mg/kg) and rivastigmine significantly increased the presence of animals in target quadrant in probe trial on the 8th day compared to hyoscine. Crocin (20 mg/Kg) increased significantly BDNF and CREB protein and transcript levels compared to hyoscine. Conclusions: Crocin improved memory impairment induced by hyoscine through reduction of the latency to find the platform in the probe trial in Morris water maze test. Crocin improved memory probably due to the increase of BDNF and CREB protein and transcript levels.