High-fructose corn syrup (HFCS) is a cost-effective sweetener that has seen a marked increase in its use in developed countries. Some studies have shown that ingestion of HFCS can cause increase in body weight and body fat. Recently, we developed a new product, rare sugar syrup (RSS) made from HFCS, which can reduce the HFCS-induced obesity. As the solid element of RSS contained about 6% rare sugar D-psicose, a functional monosaccharide with no bioavailable energy, RSS might be useful as a sweetener to take the place of HFCS. Elucidation of the effects of sub-chronic feeding in rats with RSS is essential before it can be utilized as a physiologically functional food. In this study, male Wistar rats (3 weeks old) were fed diets containing 40% RSS or HFCS for 90 days. The RSS group ingested 1.31 g/kg body weight per day of D-psicose. Body weight gain and intra-abdominal adipose tissue weight were significantly lower in the RSS group than in the HFCS group. The weight of the liver and kidneys were significantly higher in the RSS group than in the HFCS group. However, no gross pathological findings were evident at dietary doses of 40% RSS or were correlated with hypertrophy of the liver and kidney. On clinical chemistry analysis, the aspartate aminotransferase and alanine amino-transferase values were significantly lower in the PS group. Therefore, the present study found no adverse effects of 40% RSS in the diet.