We examined the effect of myricetin on cell dysfunction in cytokine-induced pancreatic β cells and assessed whether Wnt signal pathway was the target of myricetin. RIN-m5f β cells were exposed to a combination of tumor necrosis factor-α, interleukin-1β, and interferon-γ, with or without myricetin pretreatment for 48 h. The cell viability, basal and glucose-stimulated insulin secretion and Wnt-signaling proteins were evaluated with methyl thiazolyl tetrazolium assay, radio immunoassay and Western blotting, respectively. The 48 h multiple-cytokine treatment decreased cell viability and glucose-stimulated insulin secretion, while increasing basal insulin secretion. Western blot analysis showed that Wnt-signaling proteins were decreased in cytokine-treated RIN-m5f cells. However, myricetin pretreatment protected against cytokine-induced cell death. In addition, myricetin (20 μmol/L) obviously decreased basal insulin secretion and increased glucose-stimulated insulin secretion in cytokine-treated RIN-m5f cells. Western blot analysis showed that Wnt-signaling proteins were increased after myricetin pretreatment. Therefore, myricetin might attenuate cell dysfunction in cytokine-induced RIN-m5F cells via the Wnt signal pathway, and the Wnt signal pathway might be used as a new target for protecting pancreatic β cells against cytokine-induced cell dysfunction and death.