The intestinal fatty acid binding protein (FABP2) is involved in lipid metabolism whereby variations in the promoter (haplotypes A/B) and exon 2 (Ala54Thr) are associated with dyslipidemia and insulin resistance. To elucidate which factors determine FABP2 expression in human mucosa, we investigated the association between fat intake, genotypes, biochemical variables, and FABP2 expression. FABP2 gene expression was assessed in duodenal specimens from 100 participants who answered a FFQ and who were genotyped and characterized for traits of metabolic syndrome and further biochemical data. Homozygotes for haplotype A tended to have lower fat intake than B-allele carriers (P = 0.066). Searching for an explanation, we evaluated the orexigenic glucose-dependent insulinotropic polypeptide (GIP) in a subset from the Metabolic Intervention Cohort Kiel. AA homozygotes had lower postprandial GIP concentrations than BB homozygotes. Duodenal FABP2 expression was correlated with (n-3) fatty acid (FA) intake in AA homozygotes (r = 0.49; P = 0.021). It was higher in AA homozygotes than in B-allele carriers after adjustment for (n-3) FA intake (P = 0.049) and was negatively correlated with serum FFA (r = -0.41; P < 0.01). Our data indicate that FABP2 expression depends on (n-3) FA intake and FABP2 genotypes. FABP2 might be involved in regulating food intake and intestinal FA utilization.