Cyclo (his-pro), controlled-energy diet, soy protein hydrolysate (SPH), and raw vegetable food (RVF) are known to improve insulin sensitivity and body weight (BW) control. Enhancement of high cyclo (his-pro) content in SPH (HCS) was performed by refluxing SPH with 1 N KH(2)CO(3) dissolved in 70% ethanol for 2 weeks at room temperature. Using this material, we examined the effects of HCS plus RVF on glucose metabolism and BW control in genetically diabetic Goto-Kakizaki (G-K) and insulin-resistant aged overweight Sprague-Dawley (S-D) rats. Thirty 7-week-old G-K rats and 18 16- to 18-month-old S-D rats were divided into 3 groups and treated with normal chow (NC), RVF diet, or HCS diet for 8 weeks. Raw vegetable food diet was made of 1:3 RVF and 2:3 NC; HCS diet was made of 1:27 portion HCS, 8:27 RVF, and 2:3 NC. Oral glucose tolerance significantly improved in both RVF- (P<.01) and HCS-treated (P<.001) G-K rats and worsened in NC-fed rats compared with the baseline values. Similarly, oral glucose tolerance also improved in aged overweight S-D rats when treated with RVF (P<.05) and with HCS (P<.01), compared with the baseline values. Although HCS diet treatment very significantly lowered fed plasma insulin levels compared with NC diet treatment in G-K rats (P<.01), RVF diet treatment alone did not decrease plasma insulin levels. In contrast, there was no change of insulin levels in overweight aged S-D rats after either RVF or HCS diet treatment. Postfeeding glucose levels in G-K rats fed RVF or HCS significantly fell, compared with the rats fed NC (P<.05). Interestingly, fasting blood glucose levels in RVF- or HCS-fed rats were very significantly lower than in NC-fed rats (P<.001). There was no change of blood glucose levels in S-D rats due to treatments with different diet. In G-K rats, food intake did not decrease during the first 3 weeks but fell very significantly from the fifth to eighth weeks with RVF (P<.01) and HCS (P<.001) treatments in G-K rats. However, food intake reduction in aged S-D rats was shown only for the HCS-treated rat group (P<.05). Water intake slightly decreased in G-K rats with either RVF or HCS treatment (P<.05) but very significantly decreased in S-D rats with HCS treatment (P<.01). Body weight gain in young G-K rats and BW in aged S-D rats significantly decreased only when rats were treated with HCS diet (P<.05). These data suggest that regular consumption of HCS diet helps to control blood glucose metabolism in diabetic G-K rats and BW control in aged obese S-D rats.