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Introduction: The mechanism of the unfavorable outcome in diabetic patients treated with intravenous thrombolysis (tPA therapy) is still uncertain. We investigated the relationship of diabetes mellitus with early and delayed recanalization after tPA therapy.Methods: Data on 165 patients from the prospective randomized control study, evaluated the efficacy of combined tPA and Edaravone therapy, were retrospectively analyzed. All patients had the middle cerebral occlusion before t-PA therapy. Based on a history of diabetes mellitus or hemoglobin A1c level of ≥6.5% on admission, all patients were classified into diabetes (D) or non-diabetes (ND) groups. The presence of arterial recanalization was assessed at 2 points: 1) early recanalization, defined as at least partial recanalization <50% within 2 h after tPA therapy; and 2) delayed complete recanalization at 24 h.Results: Among the 165 (96 men; median age, 78 [69-85] years) patients, 33 (20%) patients were classified into the D group. Age, initial NIHSS score, DWI-ASPECTS, proximal occlusion, and the onset to needle time were not different between the 2 groups (p=0.118, 0.607, 0.586, 0.258, 0.238). Early recanalization was similarly observed in the D and ND groups (61% vs. 51%, p=0.435). However, complete recanalization at 24 h was significantly infrequent in the D group (13% vs. 44%, p=0.002). This tendency was consistent in patients with as well as without early recanalization. Regarding patients with early recanalization, 4 (22%) of the 18 patients in the D group and 34 (58%) of the 59 patients in the ND group had complete recanalization at 24 h (p=0.014). Among those without early recanalization, none (0%) of the 13 patients with the D group had complete recanalization at 24 h, while 18 (30%) of the 60 patients achieved it (p=0.029). By the multivariate regression analysis, diabetes mellitus was the independent negative factor for complete recanalization at 24 h (OR 0.17, 95%CI: 0.05-0.54, p=0.002). At 3 months, there is an increased mortality rate in the D group (19% vs. 6%, p=0.038).Conclusion: Diabetes mellitus was an indicator of no complete recanalization at 24 h regardless of the early recanalization. This may explain the mechanism of the unfavorable outcome in patients with diabetes mellitus.