Chronic liver inflammation leads to fibrosis and cirrhosis, the 12th leading cause of death in the US. Hepatic steatosis, a component of metabolic syndrome and insulin resistance, can progress to liver injury and inflammation, activating immune cells. Kupffer cells, the resident macrophages in the liver, along with infiltrating macrophages, T lymphocytes, neutrophils, and dendritic cells, contribute to liver inflammation. These cells activate hepatic stellate cells, the major source of myofibroblasts in the liver. The review discusses the initiation of liver inflammation, the role of inflammatory cells, and their interaction with myofibroblasts. Liver inflammation is closely linked to metabolic disorders such as nonalcoholic fatty liver disease (NAFLD), which affects up to 40% of Western adults. NAFLD ranges from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), characterized by inflammation, cellular injury, and fibrosis. Hepatocyte steatosis results from increased de novo lipogenesis, decreased β-oxidation, and decreased VLDL secretion, leading to lipotoxicity. Free fatty acids like palmitate can induce ceramide and lysophosphatidylcholine (LPC) formation, which activate proapoptotic signaling and lead to extracellular vesicle (EV) release. EVs contain effector proteins and miRNAs that enable cell-to-cell communication and contribute to NASH pathogenesis. Inflammatory cells such as neutrophils, macrophages, and dendritic cells are involved in liver inflammation. Neutrophils are rapidly recruited to sites of acute inflammation and play a role in liver injury. Neutrophil infiltration is associated with inflammation induced by dietary carbohydrates and cholesterol, while LPS and IL-1β mainly induce intrahepatic accumulation of mononuclear cells. T helper 17 (Th17) cells produce IL-17, which promotes liver inflammation and fibrosis. MAIT cells, which are prominent producers of IL-17, are enriched in adipose tissue compared to peripheral blood in obese patients. NKT cells, which recognize lipid antigens, are enriched in mouse livers and have protective roles in alcoholic liver injury. Hepatic stellate cells (HSCs) are key players in liver fibrosis. Quiescent HSCs store vitamin A, while activated HSCs (myofibroblasts) produce extracellular matrix (ECM) components and contribute to liver inflammation. HSC activation is driven by inflammatory signals from immune cells, particularly macrophages. TGF-β1, produced by macrophages, activates HSCs and is a major fibrogenic agonist. ROS, generated by various liver injuries, contribute to fibrogenesis by stimulating collagen production in HSCs. NOXChronic liver inflammation leads to fibrosis and cirrhosis, the 12th leading cause of death in the US. Hepatic steatosis, a component of metabolic syndrome and insulin resistance, can progress to liver injury and inflammation, activating immune cells. Kupffer cells, the resident macrophages in the liver, along with infiltrating macrophages, T lymphocytes, neutrophils, and dendritic cells, contribute to liver inflammation. These cells activate hepatic stellate cells, the major source of myofibroblasts in the liver. The review discusses the initiation of liver inflammation, the role of inflammatory cells, and their interaction with myofibroblasts. Liver inflammation is closely linked to metabolic disorders such as nonalcoholic fatty liver disease (NAFLD), which affects up to 40% of Western adults. NAFLD ranges from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), characterized by inflammation, cellular injury, and fibrosis. Hepatocyte steatosis results from increased de novo lipogenesis, decreased β-oxidation, and decreased VLDL secretion, leading to lipotoxicity. Free fatty acids like palmitate can induce ceramide and lysophosphatidylcholine (LPC) formation, which activate proapoptotic signaling and lead to extracellular vesicle (EV) release. EVs contain effector proteins and miRNAs that enable cell-to-cell communication and contribute to NASH pathogenesis. Inflammatory cells such as neutrophils, macrophages, and dendritic cells are involved in liver inflammation. Neutrophils are rapidly recruited to sites of acute inflammation and play a role in liver injury. Neutrophil infiltration is associated with inflammation induced by dietary carbohydrates and cholesterol, while LPS and IL-1β mainly induce intrahepatic accumulation of mononuclear cells. T helper 17 (Th17) cells produce IL-17, which promotes liver inflammation and fibrosis. MAIT cells, which are prominent producers of IL-17, are enriched in adipose tissue compared to peripheral blood in obese patients. NKT cells, which recognize lipid antigens, are enriched in mouse livers and have protective roles in alcoholic liver injury. Hepatic stellate cells (HSCs) are key players in liver fibrosis. Quiescent HSCs store vitamin A, while activated HSCs (myofibroblasts) produce extracellular matrix (ECM) components and contribute to liver inflammation. HSC activation is driven by inflammatory signals from immune cells, particularly macrophages. TGF-β1, produced by macrophages, activates HSCs and is a major fibrogenic agonist. ROS, generated by various liver injuries, contribute to fibrogenesis by stimulating collagen production in HSCs. NOX