Co-stimulatory molecules together with leukocyte adhesion molecules are important for T lymphocyte and leukocyte-mediated inflammatory responses. We investigated the soluble costimulatory molecules CD80, CD86, CD28, and CTLA-4 and soluble adhesion molecules in plasma of 94 type 2 diabetic patients with or without nephropathy (DN and NDN) and 20 healthy controls. Plasma concentration of sCTLA-4 was significantly lower, whereas sCD28 was significantly higher in DN patients than that in control subjects (all P < 0.05). sCD28 and sCD80 were found to be positively correlated with fasting urine albumin: creatinine ratio in DN patients but not in NDN patients. Elevated soluble adhesion molecule vascular cell adhesion molecule-1 and P-selectin could be related with the disease severity of DN (all P < 0.05). Therefore, the aberrant expression of soluble co-stimulatory molecules and adhesion molecules can be related to the activation of T cells and leukocytes in the progression of inflammation in diabetic nephropathy.