Background: Inflammation of the airways is present in COPD with increased number of inflammatory cells including killer cells that lyse their target cells by two mechanisms; membranolysis in which secreted molecules such as granzymes form pores in the membrane of target cells; and apoptosis. Granzyme B has the strongest apoptotic activity of all granzymes. Aim of this work: Aim of this work was to study the relation between Granzyme B, tobacco smoking and chronic obstructive pulmonary disease. Methods: The study included 40 clinically stable COPD patients classified according to GOLD (2013) criteria into two groups; moderate (GOLD II) and severe (GOLD III) plus 40 apparently healthy control subjects (20 smokers and 20 nonsmokers). Pulmonary function results and serum levels of Granzyme B (measured by ELISA) were recorded. Results: Granzyme B levels are elevated in COPD. Cigarette smoking appears to be a direct stimulus to Granzyme B production. Granzyme B could play a role in the pathogenesis of COPD. Aging seems to be a risk factor for Granzyme B production and pathogenesis of COPD. Conclusion: Granzyme B levels are elevated in COPD. Cigarette smoking appears to be a direct stimulus to Granzyme B production. Granzyme B could play a role in the pathogenesis of COPD. Aging seems to be a risk factor for Granzyme B production and pathogenesis of COPD