The present study was performed to investigate the involvement of SNARK in physical activity levels in mice. To examine the acute effect of SNARK deficiency on voluntary running, Snark-deficient mice (Snark^+/-: n = 16) and their wild-type counterparts (Snark^+/+: n = 16) were assigned to sedentary or exercise (1-week voluntary wheel running) groups. In addition, to clarify the differences in voluntary running activity and its effect between genotypes, mice (Snark^+/+: n = 4; Snark^+/-: n = 7) were also kept in individual cages with/without a running wheel for 5 months. Unexpectedly, in both voluntary running experiments, running distances were increased in Snark^+/- mice compared to Snark^+/+ mice. Under sedentary conditions, body and white adipose tissue weights were significantly increased in Snark^+/- mice. However, no significant differences were observed between the two genotypes under exercise conditions, and the values were significantly less than those under sedentary conditions in the long-term experiment. In the short-term experiment, serum interleukin-6 level in exercised Snark^+/+ mice was the same as that in sedentary Snark^+/+ mice, whereas that in sedentary Snark^+/- mice was significantly lower than in the other groups. In contrast, serum leptin level was significantly reduced in exercised Snark^+/- mice as compared to sedentary Snark^+/- mice. The results of this study demonstrated that exposure to an environment that allows voluntary exercise promotes increased running activity and prevents obesity in Snark-deficient mice.