Honeyberry (Lonicera caerulea) has long been used as a traditional medicine in china, Japan and northern russia. Functional studies of honeyberry have mainly focused on the fruits, which have been reported to exert various pharmacological activities, including anti-inflammatory activity, with limited or no studies on the other parts of the plant, such as the leaves and branches. In the present study, the anti-inflammatory effects of extracts of the leaves (HBl), branches (HBB) and fruit (HBF) of honeyberry plant were evaluated in lipopolysaccharide (lPS)-stimulated raW264.7 cells. HBL and HBB significantly inhibited the production of proinflammatory mediators in LPS-stimulated RAW264.7 cells, and the inhibitory effects of HBl and HBB were stronger than those of HBF. HBl and HBB blocked the nuclear accumulation of p65 independently of iκB-α. HBl did not inhibit the phosphorylation of erK1/2 or p38; however, HBB effectively inhibited the phosphorylation of p38 but not erK1/2. HBl and HBB increased the expression of heme oxygenase-1 (Ho-1) protein by inducing the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (nrf2) through the activation of the reactive oxygen species (roS)/p38 pathway; the reduction in inducible nitric oxide synthase (inoS) and interleukin-1β (il-1β) expression by HBl and HBB was inhibited by Ho-1 knockdown. in addition, HBl and HBB increased the expression of activating transcription factor-3 (aTF3), and the reduction in inoS and il-1β expression by HBl and HBB was inhibited by aTF3 knockdown. collectively, HBl and HBB inhibited lPS-induced nuclear factor-κB activation by blocking the nuclear accumulation of p65, increasing Ho-1 expression through activation of the roS/p38/nrf2 pathway, and increasing aTF3 expression. Furthermore, HBB inhibited LPS-induced p38 phosphorylation. These findings suggest that HBl and HBB may have great potential as natural products for the development of anti-inflammatory drugs.