Objective:To explore the expression of differentially expressed genes (DEGs) in the hippocampus of insomnia rat model with kidney-not-storing-will type. MethodsTwenty SD rats were randomly divided into two groups:the blank group and the kidney-not-storing-will insomnia group (model group),with 10 rats in each group. The disease model was induced by subcutaneous injection of D-galactose (D-gal) combined with intraperitoneal injection of para-chlorophenylalanine (PCPA)in the kidney-not-storing- will insomnia group and the rats in the blank group were given the same volume of 0.9% NaCl solution. The transcriptome sequencing was performed on the hippocampus of the rats in the two groups,and DEGs were screened after the establishment of the rat model. Moreover,GO enrichment and KEGG pathway analysis of DEGs were carried out,and the expression of significant DEGs was verified by real-time fluorescence quantitative PCR (RT-qPCR).  Results:Compared with the blank group,there were 1 628 DEGs in the model group,of which 887 DEGs were up-regulated and 741 DEGs were down-regulated. The DEGs were mainly involved in neuro development,cell development,triglyceride metabolism,ribosomes,oxidative stress and inflammatory factors. The DEGs were closely associated with Parkinson’s disease,Alzheimer’s disease,retrograde endocannabinoid signaling transduction pathway and Huntington’s disease. Compared with the blank group,the expression of fatty acid amide hydrolase (Faah) mRNA on hippocampus was significantly down-regulated (P<0.05),and the expression of DNA topoisomerase II (Top2a) mRNA was down-regulated,but there was no statistically significant difference (P＞0.05). The expression of guanine nucleotide binding protein coding gene 3 subunit (Gnb3) and matrix metalloproteinase (MMP-9) were both significantly up-regulated (P<0.05).  Conclusion:The kidney-not-storing-will insomnia was related to nerve,metabolism and inflammation pathways. Faah,Gnb3 and MMP-9 were the DEGs in the hippocampus of rats with kidney-not-storing-will insomnia.