Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment to sites of inflammation. Raised level of MCP-1 has been widely demonstrated in the intestinal mucosa of patients with ulcerative colitis (UC), suggesting an important role of MCP-1 in the pathogenesis of UC. The –2518A/G polymorphism in the promoter region of MCP-1 gene affecting its transcriptional activation has been reported recently. In order to assess the potential role of this polymorphism in UC, we examined its distribution in 162 unrelated UC patients and 203 healthy controls. In addition, considering the gene regulatory association between interleukin-1β (IL-1β) and MCP-1, we further examined whether the gene polymorphisms between MCP-1 and IL-1β exert synergetic effects on risk of UC. Our results show that the distribution of MCP-1 genotype or allele frequencies between UC patients and controls was not significantly different; however, the association between the polymorphism of MCP-1 –2518 GG and the polymorphism of IL-1β –511 T in UC patients is significant (OR 2.062, 95% CI 1.034–4.113, P = 0.038). This is the first report describing the association between MCP-1 polymorphism and UC, and our data suggest that the MCP-1 –2518 polymorphism itself does not represent an independent genetic risk factor for UC. In contrast, the combination polymorphisms between MCP-1 and IL-1β can increase UC risk significantly, which might help us understand the molecular mechanism underlying the development of UC.