The objectives of this study were to determine the effect of herb formula HDDM, a modification of Huangdan decoction that has been shown to be effective in the treatment of glomerulonephritis and chronic renal failure, on the blood glucose levels in multiple low doses (MLD; 50 mg/kg for five consecutive days) of streptozotocin (STZ)-treated female B6C3F1 mice. Initial studies were performed to compare diabetes induction in five strains (e.g., B6C3F1, NOD, CD-1, C3H/HeN and C57BL/6) of mice by MLD-STZ, and immune changes following the treatment. The results suggested that the order of susceptibility to diabetes induction was NOD $approx$ CD-1 > B6C3F1 $approx$ C3H > C57BL/6. Furthermore, STZ modulation of T cell development, differentiation and activation might play a role in diabetes induction by MLD-STZ treatment. MLD-STZ-induced diabetes in female B6C3F1 mice was moderate, which allowed the evaluation of drug-induced protection or exacerbation of diabetes to be performed. As such, modulation of blood glucose by HDDM, which consisted of Da Huang (Radix Et Rhizoma Rhei), Huang Qi (Radix Astragali Seu Hedysari), Dan Shen (Radix Salviae Miltiorrhizae), Yin Yang Huo (Herba Epimedii), Yi Yi Ren (Semen Coicis or Coix lacryma-jobi), Mai Dong (Radix Ophiopogonis) and Shan Zhu Yu (Fructus Corni), was evaluated in MLD-STZ-treated female B6C3F1 mice. The results suggested that HDDM could lower the blood glucose levels, but it had no immunomodulatory activities. Additionally, HDDM-treated mice exhibited improved glucose tolerance. In conclusion, these studies have suggested that MLD-STZ-induced diabetes in female B6C3F1 mice is a useful model to evaluate drug modulation of diabetes, and that the herb formula HDDM possesses anti-diabetic effects.