Chronic liver inflammation leads to fibrosis and cirrhosis, which is the 12th leading cause of death in the United States. Hepatic steatosis, a component of metabolic syndrome and insulin resistance, can progress to hepatocyte injury and inflammation, which activates immune cells. Kupffer cells, the resident macrophages in the liver, and infiltrating inflammatory cells such as macrophages, T lymphocytes, neutrophils, and DCs contribute to liver inflammation. These inflammatory cells activate hepatic stellate cells, the major source of myofibroblasts in the liver. Understanding the mechanisms of inflammation and fibrosis is crucial for developing treatments for chronic liver diseases. The review discusses the initiation of inflammation in the liver, the roles of various inflammatory cells, and their interactions with myofibroblasts. Key therapeutic targets include PPARs, FXR signaling, CCR2/CCR5, serum amyloid P, ROS regulation, and Tregs.Chronic liver inflammation leads to fibrosis and cirrhosis, which is the 12th leading cause of death in the United States. Hepatic steatosis, a component of metabolic syndrome and insulin resistance, can progress to hepatocyte injury and inflammation, which activates immune cells. Kupffer cells, the resident macrophages in the liver, and infiltrating inflammatory cells such as macrophages, T lymphocytes, neutrophils, and DCs contribute to liver inflammation. These inflammatory cells activate hepatic stellate cells, the major source of myofibroblasts in the liver. Understanding the mechanisms of inflammation and fibrosis is crucial for developing treatments for chronic liver diseases. The review discusses the initiation of inflammation in the liver, the roles of various inflammatory cells, and their interactions with myofibroblasts. Key therapeutic targets include PPARs, FXR signaling, CCR2/CCR5, serum amyloid P, ROS regulation, and Tregs.