Today, the gold standard for insulin therapy is the subcutaneous injection of insulin (CSII), despite a non-physiological route of administration with suboptimal glycemic control showed in some patients. Inability of CSII therapy to prevent inflammation and oxidative stress was firstly demonstrated in vivo on treated-diabetic rats, presenting a high variability of glycogen storage associated with glycemic fluctuations. This study suggests that targeting oxidative stress and/or inflammation could help the therapeutic management of diabetic patients.