Objective: To establish a gas chromatography (GC) method for comparison of drug concentration in plasma of caffeine in normal and diabetic cognitive dysfunction rats after intragastric administration of green tea extract

and further validate its influence on diabetic cognitive dysfunction. Method: Diabete models were copied by one-time intraperitoneal injection streptozotocin (STZ) with dose of 50 mg·kg-1

after successful replication of the model

diabetic rats were intervened by gavage of caffeine and green tea extract

respectively;blood glucose value was determined once every three weeks

cognitive function was analyzed with Morris water maze experiment at the 12 week

and then GC was used to study on pharmacokinetics of caffeine in normal and diabetic cognitive dysfunction rats

and transmission electron microscopy was employed to observe ultrastructure of neurons. Result: The linear range of caffeine was 1.28-128 mg·L-1(R2=0.998)

the minimum test limit and the minimum quantitative limit were 0.7

1.28 mg·L-1

respectively.The RSD of inter-day and intra-day precision were less than 8.0%

the average method and extraction recoveries were more than 90%.The area under the curve (AUC0-t) of caffeine in normal and diabetic cognitive dysfunction rats were(46.71±4.25)

(61.2±5.44) mg·h·L-1

the half-life (t1/2) were (2.82±0.38)

(3.71±0.13) h

the peak plasma concentration (Cmax) were (13.25±2.02)

(17.12±1.08) mg·L-1

the clearance (CL) were (0.43±0.08)

(0.33±0.07) L·kg-1·h-1

respectively.Compared with the model group

the blood glucose of caffeine group and green tea extract group dropped

their cognitive ability and ultrastructure of neurons were improved. Conclusion: Metabolism of caffeine in normal and diabetic cognitive dysfunction rats has difference

and it can improve the diabetic cognitive dysfunction.This study provides a theoretical basis for clinical use of green tea and caffeine in preventing diabetic cognitive dysfunction.