Objective      To observe the changes of hydrogen sulfide (H

2

S) and cystathionine-β-synthase (CBS) in brain tissues and cognitive function in diabetic mice.       Methods      Forty C57BL/6J mice were divided into a normal group and a model group. Mouse models of diabetes mellitus were established by high fat diet with intraperitoneal injection of medium dose streptozocin (STZ). Mouse models were subdivided into groups of 4

8

12 and 16 weeks. Changes of recognition were tested by

Morris water maze. The gas level of H

2

S

CBS activity and CBS expression in the brain tissue were detected by immunohistochemistry and sensitive sulfur electrode assay. Correlation analysis was conducted.       Results      Compared to the normal group

the latency of memory of mouse models started to increase at 4 weeks (

P

0.05)

while the percentage of total time left in the target quadrant began to decrease at 8 weeks (

P

0.01). The gas level of H

2

S

CBS activity and CBS expression in the cortex of the model mice at 12 and 16 weeks were significantly lower than that in normal mice (

P

0.05). The gas level of H

2

S

CBS activity and CBS expression in the hippocampus of the model mice were significantly decreased at 8

12 and 16 weeks

as compared to the normal mice (

P

0.01). It was revealed by correlation analysis that the gas level of H

2

S and CBS activity were positively correlated with cognitive function.        Conclusion      The gas level of H

2

S

CBS activity and CBS expression are decreased in diabetic mice

and the cognitive function declines as well. Reduction of endogenous H

2

S and CBS activity may initiate or exacerbate diabetes mellitus cognitive impairment.