The intranuclear architectural protein termed high mobility group box chromosomal protein 1 (HMGB-1) has recently been identified as a potent proinflammatory mediator. The release of HMGB-1 results in the activation of macrophages and leads to an inflammatory response. In the tumor microenvironment, it is well known that there are local inflammatory reactions and the degree of inflammatory cell infiltration inside a tumor is correlated to the prognosis of the disease. In the present study, the expression of HMGB-1 in gastric cancer cells was evaluated in relation to the clinicopathological findings (n = 76), and its expression was analyzed in comparison to immune reactive cells in gastric cancer. The expression of HMGB-1 in gastric cancer cells with the intestinal type (90.7 positive cells per 200 cancer cells +/- 37.9, n = 40) was significantly increased compared to that in the diffuse type (56.8 +/- 32.7, n = 36) (p < 0.01). Secondly, HMGB-1 expression in gastric cancer cells was positively correlated with the degree of macrophage infiltration inside the tumor microenvironment (r = 0.869, p < 0.01). Thirdly, the prognosis of the low HMGB-1 group (n = 41) was significantly poorer than that of the high HMGB-1 group (n = 35, p < 0.05), although the HMGB-1 expression in cancer cells was not an independent prognostic factor. HMGB-1 expression may be one of the key factors regulating inflammatory reactions within the tumor microenvironment.