Objective To investigate the effect of ketamine on the learning and memory ability and the activity of GSK-3 beta in hippocampal neuron in juvenile rats. Methods Forty male SD rats were randomly assigned to four groups (n=10): ketamine 4-day group (group K1), ketamine 21-day group (group K2), control group I (group Cl), control group 2 (group C2).Group K1,K2 received injection intraperitoneally with ketamine 40 mg/kg, and supplemental ketamine 20 mg/kg was given when the rats displayed righting reflex upto three times. Group C1 and C2 received equi-volum normal saline. The learning and memory function were tested in each group with the Morris water maze (MWM) at 1,2,3,4 and 18,19,20,21 days after the injections, then sacrificed after 1hr from the last MWM test to obtain the hippocampus for the detection of GSK-3 beta content. Results Compared with group Cl, the escape latency in group K1 was significantly longer (p<0.01), The activity of GSK-3 beta was significantly increased in the hippocampal neurones, and there were no significant difference between groups K2 and C2. Light microscopy showed no abnormal changes in hippocampal neurones of in all groups. Conclusion The transient learning and memory hypofunction induced by intraperitoneal injection of ketamine may be related to increased activity of GSK-3 beta in hippocampal neurons.