We have previously demonstrated that advanced glycation end product (AGE)-aggregated albumin in the blood of diabetic mice induces acidification and apoptosis in mesangial cells(MCs).Our aim here is to clarify whether it could cause mesangial mitochondrial dysfunction. MCs were incubated with AGE-cholesterol aggregated albumin(ACAA),treated with TMRM(an indicator of mitochondrial membrane potential) or Caspase 3/7 reagent for apoptosis, and then analyzed by FACS.MCs were divided into 3 groups based on size and complexity; P1 small and complex, P2 large and complex, P3 small and simple.MC counts were similar in P1,P2 and P3 of the ACAA and EMEM(control) groups 3 hr after ACAA.Mitochondrial membrane potential(MMP) was 20 % higher in the ACAA group than in the EMEM group.On the other hand,MC counts in P1 were 80 % higher,and in P2 40 % lower,in the ACAA group than in the EMEM group 18 hr after ACAA.MMP in P1 was 45 % higher,and in P2 45 % lower,in the ACAA group than in EMEM group.The number of Caspase 3/7 positive MCs in ACAA group increased in P1,and total Caspase 3/7 fluorescein intensity in P1 was 3 times greater than that in P2 18 hr after ACAA.In the EMEM group,there was no difference in total Caspase 3/7 fluorescein intensity between P1 and P2.Mitochondria could be activated in MCs just after uptake of ACAA,and then gradually inactivated.Decreased MMP could lead to decreased levels of ATP and then MCs apoptosis and necrosis.