We investigated the effects of probucol and ticlopidine on circulating levels of platelet activation markers, microparticles, soluble selectins, and malondialdehyde-low density lipoprotein (MDA-LDL) in hyperlipidemic patients with or without type 2 diabetes. There were significant differences in the levels of CD62P, PAC-1, annexin V, PDMP, MDMP, sP-selectin, sE-selectin and MDA-LDL between the hyperlipidemic patients and the controls. In particular, these markers were significantly increased in hyperlipidemic patients who had type 2 diabetes. In the hyperlipidemic patients with diabetes, MDA-LDL was decreased by both monotherapy with probucol and combination therapy (probucol and ticlopidine). In these patients, CD62P, PAC-1, annexin V, MDMP, PDMP, sP-selectin, and sE-selectin were also significantly decreased after treatment. The decreases of CD62P, PAC-1, annexin V, PDMP and sP-selectin were greater combination therapy than with monotherapy. These findings suggest that administration of probucol and ticlopidine to hyperlipidemic patients with type 2 diabetes may help to prevent the development of cardiovascular complications caused by modified LDL, selectins, or activated platelets and monocytes.