Previously, we have shown that cigarette smoke affects cardiac function, hypertrophy status, and serum proteins in SH rats (abstract 912; 48th Annual Meeting & ToxExpoTM ). Here, we investigate the reversibility of these effects after smoking cessation (SC). SH rats were exposed to diluted cigarette mainstream smoke (MS) from the reference cigarette 3R4F (MS-only; 900 µg total particulate matter/day; 5 days/week) or to fresh air (SHAM) for 90 days. SC experiments covered exposure for 30 days MS + 60 days SHAM (SC-1) and 60 days MS + 30 days SHAM (SC-2). Endpoints tested were body weight, heart hypertrophy status, neutrophils in bronchioalveolar lavage fluid, expression levels of matrix metalloproteinase-1 (MMP-1) and metallopeptidase inhibitor-1 (TIMP-1). At 90 days, parameters were decreased (body weight) or increased (all other endpoints) in the MS-only group compared to both cessations groups, which, importantly, display a SHAM-like phenotype: body weight [g]: 275.9+16.8 (MS-only), 316.0±18.5 (SC-1), 311.8+19.6 (SC-2), 301.7±28.7 (SHAM); hypertrophy status [left ventricle weight (g)/tibia length (mm)]: 0.023±0.002 (MS-only), 0.020±0.001 (SC-1), 0.021±0.001 (SC-2), 0.019±0.002 (SHAM); TIMP-1 [pg/ml]: 1990.0±219.6 (MS-only), 247.0±12.4 (SC-1), 234.7±11.5 (SC-2), 270.6±19.7 (SHAM); MMP-1 [ng/ml]: 7.3±0.4 (MS-only), 3.2±0.4 (SC-1), 3.0±0.4 (SC-2), 3.8±0.6 (SHAM); neutrophil count [%]: 12.7±1.1 (MS-only), 0.7±0.1 (SC-1), 3.6±0.6 (SC-2), 0.4±0.1 (SHAM). Further endpoints are currently under investigation. Hence, this experimental format may turn out to be suitable to evaluate respiratory and cardiovascular effects of potentially reduced-risk tobacco products.