Objective:To investigate the role of survivin in the regulation of leptin expression and its sensitivity.Methods:Survivin was overexpressed in adipocytes via lentivirus, and the RNA-sequencing(RNA-seq) was used to explore the effect of survivin on the regulation of adipocyte secretory proteins. Survivin was overexpressed in the inguinal adipose tissue(iWAT) of mice by targeted injection of adeno-associated virus(AAV). The transcription levels of leptin and adiponectin were detected by realtime quantitative PCR(RT-qPCR), and the secretion levels of leptin and adiponectin in cellular supernatants and mice serum were detected by enzyme-linked immunosorbent assay(ELISA). The protein level of phosphorylated signal transducer and activator of transcription 3(STAT3) in hypothalamus was detected by Western blotting to investigate the effect of survivin on central leptin sensitivity.Results:Survivin overexpression in both 3T3-L1 and primary white adipocyte significantly down-regulated the leptin transcriptional expression without affecting the adipocyte differentiation( P<0.01). Overexpression of survivin significantly decreased leptin level without affecting the adiponectin levels in the cellular supernatant( P<0.001). Overexpression of survivin in iWAT via AAV injection, not only specifically down-regulated leptin transcriptional level in a dose dependent manner in local adipose tissue, but also led to a decrease in serum leptin level( P<0.05). In mice fed short-term high-fat diet, STAT3 phosphorylation level in hypothalamus significantly increased, suggesting improved central leptin sensitivity. Conclusion:Survivin could downregulate leptin expression and improve leptin sensitivity in high-fat diet induced obese mice.