Pinitol (3-O-methyl-D-chiro-inositol) was identified in putative insulin mediator fractions that have hypoglycemic activity, and appears to mimic the act effects of insulin by acting downstream in the insulin signaling pathway. We evaluated the effect of pinitol therapy in type 2 diabetic patients who were poorly controlled with hypoglycemic drugs, such as sulfonylurea, metformin and/or insulin. Twenty type 2 diabetic patients were enrolled in our study. Fasting glucose, fasting c-peptide, total cholesterol, triglyceride, and HDL- and LDL-cholesterol were checked before and after a 12-week pinitol treatment (20 mg kg(-1)day(-1)). All subjects continued their current medications during the study. Adipocytokines, such as adiponectin, leptin, free fatty acids, and c-reactive protein (CRP) were checked before and after pinitol treatment. After pinitol treatment, fasting glucose, post-prandial glucose levels, and hemoglobin A1c were significantly decreased (P<0.05). Fasting serum adiponectin, leptin, free fatty acid, and CRP levels did not change after pinitol treatment. In the unresponsive group, serum c-peptide levels were higher than in the responsive group. Twelve weeks of pinitol treatment altered glucose metabolism, but not lipid profiles or adipocytokine levels, in type 2 diabetic patients. Additional research is needed to define the physiological and potential therapeutic effects of pinitol administration.