In this study, the preventive effects of Radix Trichosanthis extracts (RTE) against cytokine-induced ${eta}-cell$ death were assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of ${eta}-cell$ destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with $interleukin-1{eta}$ ($IL-1{eta}$) and $interferon-{gamma}$ ($IFN-{gamma}$) resulted in a reduction of cell viability. RTE protected $IL-1{eta}$ and $IFN-{gamma}$-mediated viability reduction in a concentration-dependent manner. Incubation with RTE also induced a significant suppression of $IL-1{eta}$ and $IFN-{gamma}$-induced inducible nitric oxide synthase (iNOS) protein expression. The molecular mechanism by which RTE inhibited iNOS protein expression appeared to involve the inhibition of $NF{-kappa}B$ activation. The $IL-1{eta}$ and $IFN-{gamma}$-stimulated RIN cells showed increases in $NF{-kappa}B$ binding activityand $I{kappa}B{alpha}$ degradation in cytosol compared to unstimulated cells. However, pretreatment with RTE inhibited cytokines-induced $I{kappa}B{alpha}$ degradation and $NF{-kappa}B$ activation in RINm5F cells. Furthermore, the protective effects of RTE were verified via protection of impairment in glucose-stimulated insulin secretions in $IL-1{eta}$ and $IFN-{gamma}$-treated islets.