Objective To investigate the effect of aspirin (Asp) on cognitive function and the insulin-like growth factor-1 receptor/phosphorylated insulin-like growth factor-1 receptor (IGF-1R/p-IGF-1R) expression in the hippocampus of rats with diabetic encephalopathy, so as to analyze the protective mechanism of aspirin on brain. Methods Diabetes mellitus (DM) was induced by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg body mass). Rats were randomly assigned to four groups (n=10 animals per group), i.e. control, control + Asp, DM, and DM + Asp groups. One week after the injection of STZ, the animals in Con+Asp and DM+Asp groups were gavaged with aspirin (10 mg/ [kg·d]) for 14 weeks. Meanwhile, the control group received the same dose of noromal saline for 14 weeks, and then the cognitive function was observed by Morris water maze (MWM) test in all rats. The expressions of IGF-1R and p-IGF-1R proteins in the hippocampus of rats were examined by Western blotting analysis. Results The cognitive function of diabetic rats was improved after treated with aspirin: the escape latency of MWM test in DM + Asp group was significantly shorter than that in DM group (P< 0.01); the number of platform crossing and time spent in the target quadrant in the MWM test were significantly more in DM + Asp group compared with those in DM group (P<0.01 or P<0.05). H-E result showed that the neurons in DM + Asp group were increased compared with that in DM group. The hippocampal expression of p-IGF-1R protein in DM group was significantly lower than that in the control group (P<0.01) and aspirin treatment significantly increased p-IGF-1R expression (P<0.01). However, the IGF-1R protein levels in the hippocampus showed no significant difference between different groups. Conclusion Aspirin may protect the brain of rats with diabetic encephalopathy by regulating the IGF-1R signaling pathway.