Inflammatory bowel disease (IBD) are characterized recurrent inflammation of gastrointestinal tract. The etiology and pathogenesis this disease is currently unclear, but it has become evident that immune and genetic factors are involved in this process. The aim of this study was to determine whether gene polymorphisms: MIF-173 G/C; CXCL12-801 G/A and CXCR4 C/T exon 2 position of rs2228014 is associated with susceptibility to IBD. A total of 286 patients were examined with IBD, including 152 patients with ulcerative colitis and 134 with Crohn's disease (CD) and 220 healthy subjects were recruited from the Polish population. Genotyping for polymorphisms in CXCL12/CXCR4 and MIF was performed by RFLP-PCR. Statistical significance was found for polymorphisms CXCR4, a receptor gene for CXCL12 genotypes and alleles in CD and for genotype C/T and T allele in ulcerative colitis with respect to control. This confirms the effect of CXCL12 gene. The interplay between CXCL12 and its receptor CXCR4 affects homeostasis and inflammation in the intestinal mucosa. Three-gene analysis in CD confirmed the association of genotype GGGGCT. Statistical analysis of clinical data of patients with ulcerative colitis showed significant differences in the distribution of genotype C/T and T allele for CXCR4 in the left-side colitis. Having CXCR4/CXCL12 chemokine axis polymorphisms may predispose to the development of IBD. Activation can also be their defensive reaction to the long-lasting inflammation.