The giant panda (Ailuropoda melanoleuca), an endangered species endemic to western China, has long been threatened with extinction that is exacerbated by highly contagious and fatal diseases. Aging is the most well-defined risk factor for diseases and is associated with a decline in immune function leading to increased susceptibility to infection and reduced response to vaccination. Therefore, this study aimed to determine which genes and pathways show differential expression with age in blood tissues. We obtained 210 differentially expressed genes by RNA-seq, including 146 up-regulated and 64 down-regulated genes in old pandas (18-21yrs) compared to young pandas (2-6yrs). We identified ISG15, STAT1, IRF7 and DDX58 as the hub genes in the protein-protein interaction network. All of these genes were up-regulated with age and played important roles in response to pathogen invasion. Functional enrichment analysis indicated that up-regulated genes were mainly involved in innate immune response, while the down-regulated genes were mainly related to B cell activation. These may suggest that the innate immunity is relatively well preserved to compensate for the decline in the adaptive immune function. In conclusion, our findings will provide a foundation for future studies on the molecular mechanisms underlying immune changes associated with ageing.