Background: The inflammasome is a cytoplasmic multi-protein complex which has recently been identified in immune cells as an important sensor of signals released by cellular injury and death. Analogous to immune cells hepatic stellate cells (HSC) also respond to cellular injury and death. Our aim was to establish if inflammasome components were present in HSC, and could regulate HSC functionality. Methods: Monosodium urate (MSU) crystals (100 µg/ml) were used to experimentally induce inflammasome activation in LX-2 and primary mouse HSC. 24 hours later primary mouse HSC were stained with -smooth muscle actin (-SMA), and visualized by confocal microscopy, and TGF- and collagen1 mRNA expression was quantified. LX-2 cells were further cultured with or without MSU crystals for 24 hours in a trans-well chemotaxis assay with PDGF as the chemo-attractant. We also examined inhibition of calcium (Ca²⁺) signaling in LX-2 cells treated with or without MSU crystals using caged IP₃. Finally, we confirmed an important role of the inflammasome in experimental liver fibrosis by the injection of carbon tetrachloride (CCL₄) or thioacetamide (TAA) in wild-type mice, and mice lacking components of the inflammasome. Results: Components of the inflammasome are expressed in LX-2 cells and primary HSC. MSU crystals induced up-regulation of TGF- and collagen1 mRNA, and actin reorganization in HSCs from wild-type mice but not mice lacking inflammasome components. MSU crystals inhibited the release of Ca²⁺ via IP₃ in LX-2 cells, and also inhibited PDGF induced chemotaxis. Mice lacking the inflammasome sensing and adaptor molecules NLRP3 and ASC had reduced CCL₄ and TAA induced liver fibrosis. Conclusion: Inflammasome components are present in HSC, can regulate a variety of HSC functions, and are required for the development of liver fibrosis.