Masson’s Trichrome staining is the most robust technique to evaluate tissue fibrosis. As the name indicates, trichrome staining utilizes three dyes that stain nuclei, cytoplasm, and connective tissue fibers and help visualize fibrosis to identify the disease state. Here, we describe a detailed Masson’s trichrome staining technique utilizing two types of liver tissues harvested from C57BL/6 mice. One group of mice was fed normal chow, while the other group was fed a high-fat-fructose diet for 22 weeks and developed fibrosis. The protocol consists of tissue processing, embedding, sectioning, and staining. After the tissue sectioning is completed, it takes approximately 4 h to finish the trichrome staining.