Adipose tissue inflammation is believed to be the most important contributor to obesity associated insulin resistance and related metabolic diseases. Pogostone (PO) is a major component of the essential oil from Pogostemon cablin (Blanco) Benth., which is used as a natural additive for food flavoring. Herein, we explored the therapeutic effects and the underlying mechanisms of PO against adipose tissue inflammation. In TNF-α-induced differentiated adipocytes, PO downregulated the phosphorylation of MAPKs and the NF-κB pathway by triggering the SIRT1 activation. In vitro, PO suppressed the migratory ability of macrophages to inflammatory adipocytes and reduced inflammatory cytokine and chemokine expression in macrophages stimulated by conditioned media from differentiated adipocytes. Notably, the above effects are attributed to blocking of the MAPK and NF-κB signal activation by hampering the SIRT1 expression, as pre-treatment with an inhibitor of SIRT1-Ex527 on adipocytes abolished the anti-inflammatory effects of PO. Furthermore, PO mitigated the levels and expressions of inflammatory cytokines in the serum and epididymal adipose tissue of LPS induced mice, as well as increased the level of the anti-inflammatory cytokine IL-10 and observably inhibited the cytokine and chemokine expression in adipose tissue. PO suppressed the phosphorylation of MAPK and NF-κB signals and promoted the SIRT1 expression in adipose tissue. In summary, our results demonstrate that PO ameliorates adipose tissue inflammation through activating SIRT1, which modulates the inflammatory pathway comprising MAPK and NF-κB signals and drives the beneficial reciprocal interactions between adipocytes and macrophages. Thus, our study suggests that PO may be a bioactive constituent for treatment of obesity and related metabolic diseases by targeting adipose tissue inflammation.