In the present study, Flos magnoliae extract (FME) was evaluated to determine if it could protect pancreatic beta-cells against multiple low dose streptozotocin (MLDS) and interleukin-1 beta and interferon-gamma. Injection of mice with MLDS resulted in hyperglycemia and hypoinsulinemia, which was confirmed by immunohistochemical staining. However, the induction of diabetes by MLDS was completely prevented when mice were pretreated with FME. FME also effectively protected B-cells against cytokine toxicity, which was demonstrated by an increase in the viability of rat insulinoma RINm5F cells and by preserved insulin secreting responses to glucose in isolated rat islets. Moreover, cytokine-induced nitric oxide production and iNOS mRNA and protein expression were significantly reduced in RINm5F cells and islets that were preincubated with FME. The molecular mechanism by which FME inhibits iNOS gene expression in in vitro and in vivo appears to involve inhibition of NF-kappa B activation. Taken together, these results reveal the possible therapeutic value of FME for the prevention of type 1 diabetes progression.