Objective To observe the effects of 4-week low intensity treadmill exercise on the learning and memory, amino acid levels and the protein expression of protein kinase A(PKA), cyclic adenosine monophosphate response element binding protein(CREB) and brain-derived neurotrophic factor(BDNF) in the prefrontal cortex (PFC) of the vascular dementia (VD) rats.   Methods Thirty-nine SD rats were randomly allocated to 3 groups, sham group (sham, n=13), vascular dementia group (VD, n=13) and vascular dementia treaded with exercise group (VD+EX, n=13). Chronic cerebral ischemia model in VD group and VD+EX group rats were established by permanent ligation of bilateral, then VD+EX group rats were submitted to 4-week low intensity treadmill exercise. After exercise, spatial learning and memory ability were evaluated by Morris water maze test (MWM), glutamic (Glu) and gamma-aminobutyric acid (GABA) levels in the PFC were measured by high performance liquid chromatography(HPLC); the protein expression of PKA, CREB and BDNF in the PFC of rats were detected by Western blotting.   Results The result  of the MWM showed the average escape latency of rats in the VD group on the 1-5 days was significantly higer than sham group, the time to first find the original platform was significantly prolonged and the platform crossings decreased significantly(P<0.01). The average escape latency of rats treated with four-week low intensity treadmill exercise on the 1-5 days was significantly lower than VD group, the time to first find the original platform was significantly shortened and the platform crossings  increased  significantly(P<0.01). HPLC and Western blotting detection showed that the levels of Glu and GABA and the protein expression of PKA, CREB and BDNF in the PFC decreased significantly in VD group rats when compared with sham group (P<0.01). Glu level and the protein expression of PKA, CREB and BDNF in the PFC of rats increased significantly(P<0.05) in VD+EX group rats when compared with VD group rats, but GABA level was not significant difference (P>0.05) between the two groups.   Conclusion Four-week low-intensity running exercise improves the learning and memory ability of VD rats through enhancing the Glu level and activating PKA-CREB-BDNF signaling in the PFC of rats.