D-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that D-psicose suppresses plasma glucose increases and reduces body fat accumulation in rats. Based on acute toxicity testing in rats, D-psicose is classified as an ordinary substance (LD(50) = 16 g/kg). Elucidating the effects of long term feeding of D-psicose in rats will be essential prior to its utilization as a physiologically functional food. In this study, male Wistar rats (3 weeks old) were fed diets containing 3% D-psicose or sucrose for 12-18 months. The rats actually ingested 1.28 g/kg body weight per day D-psicose or 1.22 g/kg body weight per day of sucrose. Body weight gain and intra-abdominal adipose tissue weight in rats fed the D-psicose diet for 18 months were significantly lower than those in rats fed the sucrose diet. Relative weights of liver and kidney were significantly higher in the D-psicose group than in the sucrose group. However, no gross pathological findings were evident at dietary doses of 3% D-psicose or correlated with hypertrophy of liver and kidney. No clinical chemical test value was suggestive of overt D-psicose treatment-related toxicity. Therefore, the present study found no adverse effects at 3% D-psicose in the diet.