Objective To find the differentially expressed long non-coding RNA (lncRNA) between db/db mice that with nephropathy (DN) or not (DM).Methods In this study,3 DM db/db mice and 2 DN db/db mice proven by renal biopsy were randomly selected,and 3 healthy db/m mice as normal control group.Then,differentially expressed lncRNAs,mRNAs and their fragments per kilobase million (FPKM) in kidney samples were detected by high-throughput next generation sequencing technology.Sequencing data were analyzed to filter out the differentially expressed lncRNA,and theirfunction was preliminarily investigated by bioinformatics analysis and functional enrichment analysis to predict their target genes.Total RNAs of kidneys from these 8 mice were extracted to run real time PCR (RT-qPCR) for verifying the outcomes of the high-throughput sequencing.Results The urinary microalbumin/creatinine ratio (UACR),serum creatinine,and glomerular basement membrane thickness of DN db/db mice were higher than those of DM db/db mice (all P ＜ 0.05),while there was not significant difference in glucose between DM and DN mice.Totally 160 lncRNAs were up-regulated and 99 lncRNAs were down-regulated in kidneys of DN mice compared with those of DM mice,in which the differentially expressed lncRNAs with FPKM value≥2 and differential expression≥ 1 fold between groups were screened and verified by RT-qPCR.Finally three lncRNAs whose variation trend were consistent with the outcomes of the high-throughput sequencing were obtained.Conclusion There was a significantly different expression pattern of lncRNA between the kidneys of DN and DM mice,which may be involved in the progress of DN.