Silent information regulators (SIRTs) belong to classⅢhistone deacetylase family dependent on nicotinamide adenine dinucleotide (NAD+). SIRTs play important roles in regulating oxidative stress, inflammatory mechanisms, and senescence, etc. A large amount of proinflammatory cytokines will be produced under various internal and external stimuli and anti-inflammatory and immunologic mechanisms will be activated. But if inflammatory cytokines persistently exist in circulating system, they will eventually cause multi-organ chronic inflammation and tissue damage. As a deacetylation cofactor for SIRTs, NAD+ may reduce the production of inflammatory cytokines through regulating histones or transcription factors such as NF-κB. Knockout of SIRTs will aggravate inflammatory invasion. So SIRTs may be a potential target for the treatment of chronic inflammatory diseases. This article reviews the role of SIRTs in the occurrence of different chronic inflammatory diseases and related signaling molecules with the aim to provide novel ideas for the treatment of chronic inflammatory diseases.