Inflammation can be initiated by invading microbial pathogens. Toll-like receptors (TLRs) recognize molecular structures derived from microbial pathogens and regulate the activation of innate immunity. TLR signaling pathways trigger the activation of nuclear factor-${kappa}B$(NF-${kappa}B$) transcription factor, leading to the induction of inflammatory gene products such as cyclooxygenase-2. Here, we present biochemical evidence that the fumaryl pyrrolidinone, (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate (IPOP), previously synthesized in our laboratory inhibits NF-${kappa}B$ activation induced by TLR agonists and overexpression of two downstream signaling components of TLRs. IPOP also inhibits TLR agonist-induced expression of cyclooxygenase-2. Our results suggest that IPOP can modulate TLR-mediated inflammatory responses and, potentially, the risk of many chronic inflammatory diseases.