The innate immune system activated as a first line of response to host defense during bacterial infections and injury. It plays a key role in the initial recognition followed by the production of pro-inflammatory cytokines and chemokines to halt invading pathogens [1]. The innate immune response relies on recognition of evolutionarily conserved structures of pathogens, known as pathogen-associated molecular patterns (PAMPs), through a limited number of germ line-encoded pattern recognition receptors (PRRs) [2]. Among these, the family of Toll-like receptors (TLRs) has been studied most extensively for immune response [3]. Bacterial cell wall components such as lipopolysaccharide (LPS) are the most potent PAMPs known and responsible for the inflammatory response observed during bacterial infections. PAMPs trigger innate immune response by producing the major inflammatory cytokines such as IL-1b and IL-18 which by autocrine and paracrine manner generates a number of other cytokines leading to chronic inflammation, profound vasodilatation, organ failure and dysfunction [4-7]. IL-1b and IL-18 are essential for host defense, innate immune response, and mediate the pathogenesis of many inflammatory diseases such as sepsis [8]. Generally, cytokines such as IL-1b, IL-18 and IL-33, lack a signal peptide for the classic endoplasmic reticulum-mediated release of proteins by exocytosis, are synthesized as an inactive precursor by NF-ĸB-mediated signalosome [9]. In order to be activated, these cytokines need to be cleaved by an intracellular cysteine protease called caspase-1. For example, activation of caspase-1 cleaves 31 kDa precursor form of IL-1b into a bioactive 17kDa form [10]. However, caspase-1 is itself synthesized as a zymogen which needs to be processed in to 20 and 10 kDa subunits to form an active enzyme. Activation of caspase-1 is mediated by recently discovered multi-protein complex called inflammasome. In response to microbial stimuli or injury, a major NOD like receptor (NLR) family member assembles in a large multi-protein complex in association with ASC and pro-caspase-1 leading to autocatalytic activation of caspase-1 [11]. NLR family proteins such as NALP1, NALP3 and NALP4 (also called NLRP1, NLRP2 and NLRP4) and a cytoplasmic protein AIM2 (absent in melanoma 2; which does not belong to NLR family) recruit CARD domain containing protein called PYCARD (or ASC) and pro-caspase-1 to from active inflammasome for the processing of inflammatory cytokines [11]. Out of these known inflammasomes, NALP3 inflammasome is extensively investigated and found to be involved in a number of inflammatory pathologies. In fact, recent emerging studies indicate that inhibition of NALP3 inflammasome -mediated innate immune response could be a novel therapeutic strategy for the prevention of inflammatory complications such as sepsis, arthritis, Crohn’s disease, Alzheimer’s, gout and atherosclerosis [12,13].