Abstract： AIM: To observe the relation between the expression of Choline acetyltransferase protein and mRNA of hippocampus and the cognitive function of diabetic rats and to explore the pathogenetic mechanism of diabetic encephalopathy. METHODS : Thirty eight SD male rats were randomly divided into normal control group (group C) and diabetic model group (group D). Diabetes was induced by a single peritoneal injection of streptozotocin. Eleven weeks later, learning and memory behaviors were investigated using a spatial version of the Morris water maze test. The expression of choline acetyhransferase mRNA in hippocampus was examined by RT-PCR and in situ hybridization. The expression of choline acetyhransferase protein was examined with immunohistochemistry and Western Blot. RESULTS: Compared with group C, group D showed a significant increase in the mean time of escape latencies ( P < 0.05 ) and a decrease in percentage of stay time in the central area and the frequency of passing the original platform position ( P < 0. 05 ). Meanwhile the expression of choline acetyltransferase mRNA and protein in hippocampus of group D were significantly reduced too( P <0.05 ). CONCLUSION : It is concluded that the reduction of the expression of choline acetyltransferase protein and mRNA in hippocampus of diabetic rat may be involved in the pathological progression of diabetic eneephalopathy.