In our study, HDAC3 activity is increased several folds in the PBMCs from patients with type 2 diabetes compared to control subjects and it showed strong positive correlation with systemic TNF-α and IL-6; mRNA expressions of MCP-1, SCOS3, and HDAC3; and fasting glucose, HbA1c, and insulin resistance (HOMA-IR), while exhibited a negative association with Sirt1. This evidence concerns the gene HDAC3 and type 2 diabetes mellitus.