Type 2 diabetes mellitus (DM) is a common chronic disease. Cardiovascular disease is the most prevalent complication of DM. In the past decade, the associations of physical activity, physical fitness, and changes in lifestyle with the risk of type 2 DM have been assessed by a number of prospective epidemiologic studies and clinical trials. Several studies also evaluate the joint associations of physical activity, body mass index, and glucose levels with the risk of type 2 DM. The results of 21 prospective studies and four clinical trials demonstrated that moderate or high levels of physical activity or physical fitness, as well as changes in lifestyle (dietary modification and enhanced physical activity) could prevent type 2 DM.