<p>Fatty liver is a disease which occurs when more than 5% of excess fat is accumulated in the liver. It progresses through biochemical reactions and signal transduction in various organs, such as the intestine, liver, and immune cells. Many groups have developed fatty liver models to reproduce the complex mechanism and the interaction between multiple organs in the body, primarily focusing on animal models. However, animal models have ethical and cost issues. Furthermore, humans and animals have differences in metabolism and immune system. Thus, novel in vitro models have been pursued as an alternative to animal models. Recently, it has been shown that multi-organ-on-a-chip (MOC) allows for recapitulating the physical and chemical interactions between multiple organs, resulting in a model closer to the real human body. Here, we developed a system recapitulating the gut-liver axis, including the innate immune response which plays an important role in the progress of non-alcoholic fatty liver disease (NAFLD). To achieve this goal, we utilized novel insert modules, representing different organs, which are integrated into the main chip to allow for fluidically connected co-culture. MOC recapitulated the symptoms observed in the process of NAFLD progressing to steatohepatitis, including weakening the intestinal wall, oxidative stress, and inflammation. This MOC can be used as a model to evaluate the effects of drugs or food components on the intestines and livers. We envision that it can also be used to evaluate how the inflammatory response in the intestine, liver, and blood vessel affects the pathogenesis of liver disease.</p>