Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Preclinical models of COPD have recently been developed. In those models, COPD/emphysema has been commonly induced using different toxic agents such as elastase, proteolytic enzymes and chronic exposure to cigarette smoke (CS). Areas covered: The most relevant features of preclinical models of COPD, namely chronic exposure to CS and other agents (proteases and microorganisms), cardiovascular effects, surfactant protein-D, airway remodeling and inflammation, lung regeneration potential and mesenchymal stromal cell therapy are described. The most relevant publications on the topic of interest were selected from Pubmed. Expert opinion: Preclinical models of COPD are key for understanding the underlying biology and pathophysiology of the disease and for the discovery of therapeutic targets. Enhanced biological insights will help discover therapeutic targets for the treatment of COPD. This will enable health caregivers and doctors to improve treatment where a more holistic approach will be used. This will benefit the patients and society because the use of resources should be significantly lowered.