Introduction: Physical activity has been found to be related with many health benefits. Our aim was to investigate ameliorative effect of chronic moderate exercise from acute stress on nicotine and cigarette smoke exposed rats. Methods: Male Sprague-Dawley rats were used (n=48). Nicotine bitartarate was applied intraperitoneally (0.1 mg/kg/day) to a group of rats for 5 weeks, another group was exposed to cigarette smoke in a ventilated chamber. After 1 week of nicotine application or smoke exposure, moderate exercise training protocol was applied to exercise groups. At the end of the experiments, acute stress induction were made to all groups by electric foot shock protocol. For determining the anxiety levels Hole-board tests were performed before and after the experiments. For measurement of tissue superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione (GSH) and myeloperoxidase (MPO) levels and for histological analysis lung, liver, colon, stomach and gastrocnemius tissues were collected. Results: MDA levels were increased in all tissues of smoke exposed group (p<0.05-0.01) except gastrocnemius tissue compared to control group, and were decreased with exercise (p<0.05-0.001). MPO levels were increased in lung, liver and colon tissues of smoke exposed group (p<0.05-0.001) and liver and colon tissues of nicotine applied rats (p<0.01-0.001) and decrease with exercise in liver and colon tissues of both smoke exposed or nicotine applied groups (p<0.05-0.01).In all tissue samples, increased histological injury scores in smoke exposed and nicotine applied groups (p<0.05-0.001) decreased significantly with exercise (p<0.01-0.001). Conclusion: Biochemical parameters and histological scoring indicated increased tissue injury due to nicotine application and cigarette smoke exposure and exercise training ameliorated these effects in most of the tissues of acute stress induced rats.