iHSP72 expression in skeletal muscle of T2DM patients was positively correlated with insulin sensitivity, and adiposity was negatively correlated with iHSP72 expression. Serum eHSP72 was positively correlated with disease duration and positively correlated with inflammatory markers (CRP, TNF-α). In T2DM, the imbalance between iHSP72 down-regulation and eHSP72 up-regulation reflects the pathological role of obesity and inflammation, and targeting the HSP70 pathway may provide a new strategy for the treatment of diabetes and its complications. This evidence concerns the gene HSPA1A and obesity due to melanocortin 4 receptor deficiency.