The recent emergent coronaviruses in the 21st century, such as Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV), Middle East Respiratory Syndrome- Coronavirus (MERS-CoV), and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has caused significant morbidity and mortality around the world. The lung is the most affected organ in the infection of human pathogenic coronaviruses. There is always a scarcity of human signs, symptoms, and modes of transmission. So to study the viral pathogenesis and evaluated interventions of therapies and vaccines, animals need to be used as models, especially at early epidemics. Lesions scoring can be identified from histopathological studies, and it can be helpful to understand the viral pathogenesis and damages to the cells to design effective therapies or vaccines. Histopathology uses the cells to determine viral host receptors and viral host tropism to relate with disease severity and lesions. Moreover, histopathology also plays a role in the qualitative description of affected organs to determine the micro-anatomic location of cells, type of cells, and cellular consequences during and post-infection. Comparatively, this approach has various limitations, but still, it is significant in comparing treatment groups. In comparing various groups, semi-quantitative and quantitative tissue scores are used for statistical analysis to increase the reproducibility of the study. This chapter refers to different features, including the importance of histopathology, principles, technique, scoring methods, and pathological characteristics of COVID-19, which can be valuable to assess the lung infection caused by SARSCoV- 2 and animal models and real situations.