AIM: To explore the effects of naloxone on spatial learning and memory ability and its possible mechanism for vascular dementia(VD) rats. METHODS: The rats models of vascular dementia were made by permanent bilateral occlusion of both common carotid arteries (2 VO methods). The models were then divided into three groups at random: sham-operated group, model group and naloxone preventive treatment group. Naloxone group was successively received naloxone treatment(naloxone hydrochloride, 0.8 mg·kg -1 ·d -1 , ip) for 7 d after the operation immediately, while the other two groups were received equal volume of saline, ip. All of the rats were trained in Morris Water Maze (MWM) regularly for 5 d to find the escape latencies(EL) after 8 wk of the operation and then followed by a comparison of the learning and memory differnce in three groups. Laser scanning confocal microscope and Fluo-3 were used to measure intracellular calcium fluorescence pixel values of the hippocampal neurons. RESULTS: The EL in model group was significantly longer than that in sham-operated group(P<0.01), but the times of passing through the platform were signicantly decreased(P<0.01). The EL of naloxone group was significantly shorter than that of model group (P< 0.01 ) and the times of passing through the platform were signicantly increased (P< 0.01). Additionally, The fluorescence pixel value of intracellular calcium of hippocampal CA1 region neurons in model group(484±299) was significantly increased (P<0.01); but in naloxone group the fluorescence pixel value of intracellular calcium of hippocampal CA1 region neurons (139±31) was significantly decreased (P< 0.01 ). CONCLUSION: The promoting effects of naloxone on spatial learning and memory deficits in rats with VD are significant. Its mechanism may be connected with the preventing calcium increase in hippocampal neurons by naloxone.