A total of 60 middle-age and aged (above 10 years) Cynomolgus Monkeys (Macaca fascicularis) with normal fasting plasma glucose (FPG) values (3.20 mmol/L≤FPG<5.50 mmol/L) were fed by high energy diet for twelve months. After feeding, they were classified into two groups, normal FPG group and induced high FPG group (FPG≥5.50 mmol/L). Diabetes-associated gene expression profiles of peripheral blood leukocytes of the two groups were analyzed using quantitative real-time PCR before and after high energy diet, respectively. The results showed that FPG and triglyceride (TG) of induced high FPG group were strikingly higher than normal FPG group (P<0.05), but there was no significant difference in high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), cholesterol (TCHO) between the two feeding groups (P>0.05). Among 36 diabetes-associated genes tested, 19 genes (including angiotensin I converting enzyme (ACE), phosphorylase, glycogen, liver (PYGL), aquaporin 2 (AQP2)) displayed a similar expression pattern between induced high FPG group and normal FPG group and they were significantly up-regulated or down-regulated after high energy diet feeding (P<0.05), while expression variation of all these 19 genes were stronger in induced FPG group compared to normal FPG group. The expressions of ATP-citrate lyase (ACLY), selectin-L (SELL), synaptosomal-associated protein 23 (SNAP23) and syntaxin 4A (STX4) were significantly different only in induced high FPG group (P<0.05).