It is known that clinic blood pressure (BP), gender, cigarette smoking, dyslipidemia, anemia and thiazolidenediones (TZD) treatment are predictors for clinically significant diabetic macula edema (CSDME). We examined a most risky factor for CSDME in Japanese patients with type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) confirmed using optical coherence tomography by multiple regression analysis (MRA). As the risk factors, wakening-up BP was added to such factors. Seven diabetic Japanese patients with CSDME (group 1) and 124 subjects without CSDME (group 2) assonated with DR using optical coherence tomography were studied. The durations of T2DM in groups 1 and 2 were 15±10 years and 20±15 years, respectively. There was no statistically difference in means of gender, duration, age, body mass index (BMI), HbA1c, TC, LDL and TC/HDL, serum creatinine, urinary albumin excretion rate, and clinic BP between two groups. Morning systolic home BP (MSHBP), cigarette smoking and foveal thickness were significantly (p<0.001) higher in group 1 than group 2, whereas visual acuity was significantly (p<0.00?) lower in group 1 than in group 2. The patients in both groups had received various kinds of drugs for hyperglycemia, hypertension and others. There were no significant differences in the variables in both groups. MRA revealed that MSHBP, cigarette smoking and pioglitazone as TZD treatment were significantly positive predictors for CSDME, while BMI had a significantly negative predictor. Other variables were not significantly correlated to CSDME. The review summarizes a multiple regression analysis revealed that MSHBP makes an addition to predictive factors for CSDME among risk factors reported previously in patient with T2DM.