Objective: To explore the anti-inflammatory mechanism of zeaxanthin (ZEA， a natural carotenoid) based on the NF-κB signaling pathway in lipopolysaccharide-induced (LPS-induced) 3T3-L1 adipocytes chronic inflammatory. Methods: The inflammatory models were established by using LPS to stimulate mature 3T3-L1 adipocytes and were intervened with different concentrations of ZEA (0， 5， 10， 15 μmol/L). The content of inflammatory-related cytokines was measured， and their mRNA expression levels were detected by Quantitative Real-time PCR (qPCR). In addition， the mRNA and protein expression levels of signaling pathway cytokines were detected by Western blot. Results: Compared with the normal group， ZEA intervention significantly down-regulated the secretion of pro-inflammatory cytokines IL-1β， IL-6， TNF-α and MCP-1 (P＜0.001) while up-regulated the content of anti-inflammatory cytokines IL-10 and ADPN (P＜0.001) in the inflammatory models. Moreover， qPCR indicated that ZEA inhibited the mRNA expression of pro-inflammatory cytokines (P＜0.001) while recovering the mRNA expression of anti-inflammatory cytokines (P＜0.001). Furthermore， Western blot analysis suggested that ZEA notably decreased the protein and phosphorylation expression of catalytic subunits of IκB kinases (IKKα and IKKβ) (P < 0.001)， then increased the combination of inhibitory protein IκBα and nuclear transcription factor NF-κB p65， and eventually inhibited the transcription of NF-κB p65 in the nucleus. Conclusions: Zeaxanthin effectively alleviates obesity-caused chronic inflammation by inhibiting NF-κB signaling pathway activation and regulating inflammatory cytokines secretion.