Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and cognitive deficit. The observed amnesia in the early stages of AD is suggested to be a retrieval problem, rather than encoding and consolidation deficit. According to the cholinergic hypothesis of AD, scopolamine is used to induce an animal model of amnesia. Howbeit the effect of scopolamine on memory retrieval is contradictory. This study aimed to assess the effect of scopolamine on passive avoidance memory retrieval. Additionally according to the reported changes of MMP-2, MMP-9 and MAPKs (ERK, P38 and JNK) in AD pathology the hippocampal contents of these proteins were determined. Male NMRI mice weighing 20–25 g were trained in passive avoidance apparatus. The drug or its vehicle was injected 24 h after training (30 min before retention test). The hippocampal tissue was isolated and western blot analysis was done for MMP-2, MMP-9 and MAPKs (ERK, P38 and JNK). The results indicated that scopolamine (1 mg/kg) disrupts passive avoidance memory retrieval. This scopolamine treatment resulted in hippocampal MMP-2 and MMP-9 decline while increased MAPKs in the hippocampus. These results suggest that cholinergic system has an important role in learnt memory retrieval. It might also suggest the positive role of MMP-2 and MMP-9 in this phase of memory while propose that MAPKs affect negatively the reactivation of memory which is compatible with MAPKs activation in AD.