Previously, the aqueous ethanolic extract (AEE) of unripe fruit of bitter melon (BM; Momordica charantia) was demonstrated to inhibit cytokine-induced apoptosis via modulating Bcl-2 family and caspase cascades in MIN6N8 pancreatic ${eta}$-cells. Here, it was sought to determine whether the anti-apoptotic effect of AEE-BM is mediated by suppressing the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-${kappa}B$ (NF-${kappa}B$), major upstream effectors of Bcl-2 family and caspase cascades, in cytokine-treated MIN6N8 cells. The results exhibited that the AEE-BM suppressed the activation of MAPKs including stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), p38, and p44/42, and the activity of NF-${kappa}B$. The findings suggest that BM protects pancreatic ${eta}$-cells through down-regulation of MAPKs and NF-${kappa}B$.