Pueraria lobata (Willd.) Ohwi was investigated to check its modulatory effects on the activation of macrophages upon inflammatory conditions treatment. For this purpose, we examined several inflammatory responses such as nitric oxide (NO) production, reactive oxygen species (ROS) generation, cytoprotection and phagocytosis under the treatment of methanol extract from P. lobata (Pl-ME). Pl-ME dose-dependently blocked NO production in lipopolysaccharide (LPS)- stimulated RAW264.7 cells but not sodium prusside (SNP)-generated NO release. The NO inhibition seemed to be due to blocking inducible NO synthase (iNOS), since Pl-ME suppressed its expression in a NF-${kappa}B$-independent manner. Similarly, this extract also effectively protected RAW264.7 cells from LPS-induced cytotoxicity. However, Pl-ME did not block ROS generation and rather it enhanced. Finally, this extract negatively modulated FITC-dextran uptake. Therefore, our data suggested that Pl-ME may be involved in negatively regulating some macrophage-mediated inflammatory responses such as NO production and phagocytic uptake.