Patients with diabetes mellitus are easy to experience diabetic encephalopathy 
(DE) and other cognition dysfunction, whereas the neural alterations in 
developing this disease are unknown yet. Chrysophanol (CHR) is one of 
traditional Chinese medicine which was reported to show protective effects in 
cognition dysfunction and inflammatory in previously studies. In this current 
study, whether CHR protects learning and memory dysfunctions induced by diabetes 
disease or not and underlying mechanisms were studied. DE model was induced by 
streptozotocin (STZ, i.p.) in ICR mice. CHR was administrated 3 days after STZ 
treated mice which was confirmed with diabetes for consecutive 6 days. Learning 
and memory function was tested by Morris water maze after the CHR injection. The 
morphology of neuronal cells in hippocampus CA3 region was stained by 
HE-staining. ELISA and Western blot assay were used to determine the levels of 
pro-inflammation cytokines (IL-1β, IL-4, IL-6, TNF-α) in hippocampus. Here, we 
demonstrated that mice harboring diabetes mellitus induced by STZ exhibit high 
blood glucose, learning and memory deficits detected by Morris water maze 
behavior tests. Application with CHR right after developing diabetes disease 
rescues partial blood sugar increasing, learning and memory deficits. The data 
also indicated that the death rate of neurons and the number of astrocytes in 
hippocampus CA3 region was significantly improved in diabetic mice. Moreover, 
the underlying mechanisms of CHR's protective effect are likely associated with 
anti-inflammation by downregulating the expression of pro-inflammation cytokines 
(IL-1β, IL-4, IL-6, TNF-α) in hippocampus and inhibiting the over-activation of 
astrocytes in hippocampus CA3 region. Therefore, application with CHR 
contributes to the learning and memory deficits induced by diabetes disease via 
inhibitory expressions of inflammatory in hippocampus region.