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