Plastic bag is an important product of the petrochemical industry, has become an indispensable daily necessities. In Taiwan, plastic bag is a very convenient way to carry hat food. However, heated plastic bags would release toxic substances for endangered the environment and the health of the people. This study aims to evaluate whether high density polyethylene (HDPE) plastic bags water extract could release inflammatory mediator in murine RAW264.7 macrophages. HDPE plastic bag boiled for 30 minutes, then DMEM cultured medium contained the extract water to culture macrophages. We found that the medium would induce proinflammatory cytokine productions (IL-6, TNF-α), and increased nitric oxide release in activated macrophages. We also found that the extracted medium increase iNOS and COX2 expression, and activated the phosphorylation of NF-κB and ERK1/2. These results suggest that water extract of HDPE plastic bag induce inflammatory effect by stimulated of NF-κB and ERK1/2 pathways that increased the levels of proinflammatory cytokines and mediators in RAW264.7 cells.