Cigarette smoking is a major risk factor for the development of respiratory diseases. Several observations suggest that different genders may have a different susceptibility for lung diseases. Sex differences in regards to exposure susceptibility and sensitivity may be present because of morphological differences between female and male lungs and/or may be due to the effects of differences in levels of sex hormones. For example adult female rats have more and smaller alveoli than males thereby providing them with larger alveolar surface area to body mass ratios, whereas adult male mice have larger absolute lung volumes than females but smaller volume to body mass ratios which likely influence the response to inhaled toxicants. In order to gain insights into the sex-related differences in response to cigarette mainstream smoke (CS), a 90-day rat inhalation study, as described in the Organization for Economic Co-operation and Development (OECD) guideline 413, was augmented with multi-analyte profiling of the bronchoalveolar lavage fluid (BALF) and transcriptomics analysis of lung tissue. The comparison between female and male rats in regard to some respiratory-related endpoints are shown here.