Previous studies have demonstrated that voluntary wheel running improves learning and memory capabilities in rodents. In this study, we further investigated whether chronic treadmill exercise improved hippocampus-dependent learning/memory capabilities and upregulated neural plasticity-related genes in the hippocampus. Male C57BL/6 mice (3 months old) were divided into control and exercise groups. The exercised animals received treadmill running for 60 min/d, 5 d/wk for 4 or 12 weeks (speed: 10-12 m/min). At the end of the experiments, one-trial passive avoidance tasks or Y maze tests were executed to evaluate learning and memory behaviors. The animals were then humanely killed. The mRNA and protein expressions of dopamine receptor D1 and plexin A1, an axon guidance molecule, in the hippocampus were determined by real-time PCR and Western blotting techniques, respectively. The results were analyzed by unpaired Student’s t test (statistically significant if P<0.05). Our preliminary results showed that 1) 4- or 12-week treadmill running improved learning and memory capabilities, indicated by increases in passive avoidance retention latency and the novel arm entry probability of the Y maze task; 2) exercise tended to elevate gene expressions of D1 and plexin A1 in the mouse hippocampus. In conclusion, chronic treadmill exercise improves the capabilities of learning and memory, possibly due to an increase in hippocampal neural plasticity-related gene expression.