We have examined thrombin-induced metabolism of phosphoinositides in the platelets from fifteen NIDDM (non-insulin-dependent diabetesmellitus) patientsandfifteen healthy subjects (control) The diabetic patients were divided into two groups. One group (group I) had diabetic retinopathy (microangiopathy) and the other group (group II) had atherosclerosis of great vessels (macroangiopathy). In platelets incubated with [³²P] orthophosphate for 80min, the incorporation of ³²P radioactivity into phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol 4, 5-bisphosphate (PIP₂) was significantly lower in the group II than in the control. The addition of thrombin induced a marked decrease in PIP₂ radioactivity at 10 sec in platelets from group I compared with that from the control. These results suggest that the breakdown of polyphosphoinositides is increased in platelets from diabetic subjects with retinopathy, and also that the formation of polyphosphoinositides is decreased in the platelets from diabetic subjects with macroangiopathy.