Infection-associated chronic inflammation plays an important role in tumorigenesis, and macrophages are a key player in both inflammation and tumorigenesis. Tumor-associated macrophages accelerate tumorigenesis through the enhancement of angiogenesis, remodeling and the suppression of antitumor immunity. Helicobacter pylori infection induces inflammatory responses, which are closely associated with gastric cancer development. Recent studies using mouse models indicate that activated macrophages in the infected and inflamed gastric mucosa express TNF-alpha, which stimulates the surrounding epithelial cells to promote Wnt signaling activity. Such a promotion of Wnt signaling activity beyond the threshold for tumorigenesis may, therefore contribute to gastric cancer development. Accordingly, it is possible that the TNF-alpha-induced promotion of Wnt signaling is a novel protumorigenic mechanism of inflammation in gastric carcinogenesis.