BACKGROUND: Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. PPARgamma-coactivator 1 (PGC-1) and Peroxisome proliferator -activated receptors (PPARs) costimulate the expression of key enzymes of gluconeogenetic pathway. This study was performed to evaluate the response to dietary caloric restriction (CR) on the PPARs and PGC-1 expression in liver of diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Diabetic OLETF rats (male, 24 weeks) and Long-Evans Tokushima Otsuka (LETO) rats (male, 24 weeks) were used in this study. Liver PPARs and PGC-1 mRNA, and blood glucose levels were investigated at 1, 2, and 3 weeks after the beginning of 30% CR. PPARs and PGC-1 mRNA were determined by RT-PCR and blood glucose levels were measured by spectrophotometric assay. RESULTS: The liver PGC-1 mRNA expressions were increased to 19% in non-diabetic LETO rats but significant change was not observed in diabetic OLETF rats by 30% CR. The liver PPARgamma mRNA expressions were not changed in non-diabetic LETO rats but increased to 23% in diabetic OLETF rats by 30% CR. The difference of PPARalpha and PPARbeta mRNA expressions in liver of OLETF and LETO rats were not observed. CONCLUSION: The liver PPARgamma and PGC-1 expression response to CR are altered in OLETF rats compared to in LETO rats. These findings suggested that PPARgamma and PGC-1 expression control system altered in diabetic OLETF rat liver and altered PPARgamma and PCG-1 expression may some roles on the aberrantly activated gluconeogenesis in diabetes mellitus.