Epidemiological data suggest that a sedentary lifestyle may contribute to increased susceptibility for some environmental toxicants. We developed an animal model of active versus sedentary life style by providing female Sprague-Dawley rats with continuous access to running wheels. Sedentary rats were housed in standard cages without wheels. After training for 12 wks, rats were exposed to 0, 0.25, 0.5 or 1.0ppm ozone [O-3 for 5 h/d, 1 d/wk, for 6 wk (N = 10 per group)]. Body composition (%fat, lean and fluid) was monitored noninvasively over the course of the study. Ventilatory parameters [tidal volume, minute ventilation, frequency and enhanced pause (Penh)] were assessed using whole-body plethysmography prior to O-3 and 24 h after the 5th O-3 exposure. Trained rats lost similar to 2% body fat after 12 wk of access to running wheels. Peak wheel activity was reduced by 40% after exposure to 1.0ppm O-3. After the 5th O-3 exposure, body weight and % fat were reduced in sedentary but not trained rats. Penh was significantly elevated in sedentary but not trained rats the day after exposure to 1.0 ppm O-3. However, lung lavage cell counts and biomarkers of pulmonary inflammation measured 1 day after the final exposure were inconsistently affected by training. Wheel running led to marked physiological responses along with some indication of improved pulmonary recovery from O-3 exposure. However, wheel running with O-3 exposure may also be a detriment for some pulmonary endpoints. Overall, a sedentary lifestyle may increase susceptibility to O-3, but additional studies are needed.