Uncaria rhynchophylla (UR) is an herbal plant that has been used widely to treat stroke, hypertension and atherosclerosis. Upregulated heme oxygenase-1 (HO-1) plays a crucial role in cytoprotection and anti-inflammatory responses in a variety of pathological models. In this study, we investigated upregulation of HO-1 by UR, which is inducible and cytoprotective enzyme in RAW 264.7 macrophages. Upregulation of HO-1 and signal pathways were examined by western blots, RT-PCR and immunofluorescence staining. Treatment of UR induced HO-1 protein expression and Nrf2 nuclear translocation in RAW 264.7 macrophages. HO-1 induction was strongly inhibited by the suppression of p38 MAPK and ERK activity. Additionally, rottlerin, an inhibitor of protein kinase $C{delta}$(PKC ${delta}$), abolished the upregulation of HO-1 protein levels. From the above results, it is suggested that UR may exert a cytoprotective effect via the upregulation of HO-1 in RAW 264.7 macrophages.