Objective To investigate the effects of apigenin（ Apg） on cognitive impairment in KKAy mice， a model of type 2 diabetes（ T2DM）， and explore its potential mechanisms. Methods Bioinformatics analysis was performed to identify overlapping target genes of Apg， T2DM， and cerebral small vessel disease （CSVD）. Protein-protein interaction（ PPI） analysis， Gene Ontology（ GO）， and Kyoto Encyclopedia of Genes and Genomes（ KEGG） pathway enrichment were conducted using the DAVID database. Ten-week-old SPF grade spontaneous type 2 diabetic KKAy mice weighing（ 36±3） g were selected. KKAy mice were randomly divided into four groups（ n=10 per group）： T2DM model group（ Model group）， and low-（ 3 mg/kg）， medium-（ 6 mg/kg）， and high-dose（ 12 mg/kg） Apg intervention groups（ intraperitoneal injection）. Additionally， 10 C57BL/J mice served as the blank control group（ Control group）. Cognitive function was assessed using the Morris water maze test. The Apg group， which showed the most significant cognitive improvement， was selected for further experiments， including RT-PCR， inflammatory factor detection， and Western blotting. Neuronal apoptosis， tumor protein 53（ TP53）， interleukin-6（ IL-6）， tumor necrosis factor-α（ TNF-α）， I L-1β， B-cell lymphoma-2 （Bcl-2）， Bcl -2-associated X protein（ Bax）， and caspase-3 expression levels were measured. Results TNF-α and TP53 were identified as key target genes， with downstream interactions mainly involving Caspase and Bid family proteins. The MWM test showed that mice in the high-dose Apg group exhibited significantly increased platform crossings［ （4.42±0.76） vs.（ 1.80±0.41） times， t=9.59， P＜ 0.05］ and longer residence time in the target quadrant［ （33.5±6.1） vs.（ 16.1±4.1）s， t=7.49，P＜ 0.05］ compared with the Model group， indicating improved cognitive function. Thus， the high-dose group was selected for subsequent studies（ named as Apg group）. Further experiments showed that compared with the Model group， Apg intervention significantly reduced the expression of TNF-α［ （50.4±9.6） vs（. 29.3±7.1） pg/ml， t=6.28， P＜0.01］， IL-1β［ （60.4±13.6） vs（. 28.7± 7.1） pg/ml， t=6.56， P＜0.01］， IL-6［ （3.4±0.5） vs（. 1.8±0.3），t=5.58，P＜0.01］ and TP53［ （4.4±0.9） vs（. 2.3±0.4）， t=6.18， P＜ 0.01］ in mouse hippocampus. It also decreased the expression of Bax［ （2.74±0.60） vs.（ 1.60±0.30）， t=5.18， P＜0.05］ and Caspase-3 proteins［ （3.14±0.60） vs（. 1.80±0.40）， t=5.58， P＜0.05］， increased Bcl-2 protein expression［ （0.61±0.10） vs.（ 0.78±0.10）， t=4.46， P ＜ 0.05］， and reduced neuronal apoptosis ［（30.4±5.6）% vs.（ 18.0±2.1）%， t=6.56， P ＜ 0.01］. Conclusions Apg may exert neuroprotective effects against T2DM-induced cognitive impairment through anti-inflammatory（ downregulating TNF-α， IL-1β， IL-6）， anti-apoptotic（ regulating Bax/Bcl-2/Caspase-3）， and TP53 signaling pathway modulation mechanisms.