The objective was to study neuronal apoptosis and changes in the proteins related to the mitochondrial pathway in the hippocampus of a rat model of Alzheimer’s disease (AD) and discuss its significance in AD. Thirty-six Sprague-Dawley rats were divided into 3 groups: a normal group, a control group and an AD group. AD was established by injecting β-amyloid1–42 (Aβ1–42) into the hippocampus. Learning and memory ability was estimated with a Y maze at different times. The apoptotic neurons were detected by the TdT-mediated X-dUTP nick end labeling (TUNEL) method. Cytochrome C and caspase-9 protein expression in the hippocampus was detected by Western blot. The results showed that there was obvious impairment of learning and memory in rats of the AD group after Aβ1–42 injection. The apoptotic neurons in the hippocampus of the rats in the AD group were significantly increased compared with the normal group and the control group (p < 0.01), and the expression of cytochrome C and caspase-9 in hippocampus in AD group was significantly increased too (p < 0.01). The results suggest that the mitochondrial pathway is one of the important neuronic apoptotic pathways induced by Aβ1–42 in the hippocampus, and may play an important role in the pathogenesis of AD.