Objective To investigate the effect of streptozotocin (STZ) on learning,memory and expression of p-MKK4,p-JNK and p-Jun in APP transgenic mice.Methods Three-month-old APP/PS1 mice were intraperitoneally injected with STZ.Learning and memory function was performed by Morris water maze.The changes of neuronal morphology in hippocampum were observed by Nissl staining.The expression of MKK4,JNK and c-Jun were detected in hippocampal tissues by Western blotting.Results In the hidden platform experiment of Morris maze,the escape latencies and the pathway length of STZ-induced diabetic mice were longer than those in controls from the 2nd to 5th day(P ＜ 0.05 or P ＜ 0.01).The Nissl staining showed that some neurons in hippocampum of STZ-treated mice were displayed changes of injury.Compared with the vehicle control,the expression levels of pJNK and p-c-Jun were increased by 217.78 ± 23.49 and 189.27 ± 17.80,respectively (P ＜ 0.01).Conclusion STZ can decrease the learning and memory function and injury the neurons,which maybe relate to the JNK signal pathway.