Abstract: This study is to investigate the protective effect of mangiferin on NF-κB (P65) and IκBα expression in peripheral blood mononuclear cell (PBMC) in rats with cigarette smoke induced chronic bronchitis. The rat model with chronic bronchitis was established by cigarette smoke. Real-time fluorescence RT-PCR was executed for evaluating the NF-κB (P65) and IκBα gene expression in mononuclear cell, and flow cytometry for their protein expression. The serum hs-CRP (high-sensitivity C-reactive proteins) and TNF-α (tumor necrosis factor-α) were detected by enzyme-linked immunosorbent assay. The histopathological score was obtained from lung tissue HE staining slides of lung tissue. The results showed that mangiferin could markedly suppress the NF-κB (P65) mRNA and protein expression in mononuclear cell, while promote the IκBα mRNA and protein expression. Furthermore, mangiferin could lower serum hs-CRP and TNF-α level, and reduce the chronic inflammatory damage of bronchiole. These results suggested that mangiferin could notably ameliorate chronic bronchiole inflammation induced by cigarette smoke, and this protective effect might be linked to the regulation of NF-κB (P65) and IκBα expression in mononuclear cell.