IL-4 and IL-13 are pleiotropic cytokines whose biological activities overlap with each other. IL-13 receptor α chain 1 (IL-13Rα1) is necessary for binding to IL-13, and the heterodimer composed of IL-13Rα1 and IL-4R α chain transduces IL-13 and IL-4 signals; however, the functional mapping of the intracellular domain of IL-13Rα1 is not fully understood. In this study, we constructed wild and mutated types of human IL-13Rα1, and analyzed IL-4 and IL-13 signals using an IL-13Rα1-transfected human B cell line. Expression of IL-13Rα1 evoked STAT3 activation by IL-4 and IL-13, and in stimulated human B cells, on which IL-13Rα1 was highly expressed, IL-4 and IL-13 induced STAT3 activation. Replacement of the two tyrosine residues completely abolished STAT3 activation, although replacing either tyrosine residue alone retained it. Furthermore, we found that the Box1 region and the C-terminal tail of IL-13Rα1 were critical for binding to Tyk2, and activation of Jak1, Tyk2, the insulin receptor substrate-1 and STAT6 respectively. These results suggest that STAT3 activation is involved with IL-4 and IL-13 signals in human B cells along with the activation of STAT6, and that there is a unique sequence in IL-13Rα1 to activate STAT3.