ABSTRACT. We aimed to investigate the effect of two common polymorphisms in interleukin-4 (IL-4) on serum IL-4 levels and the development of ankylosing spondylitis (AS) in the Chinese population. A total of 420 inpatients and outpatients diagnosed with AS were enrolled as the case group, and 330 healthy volunteers were selected as the control group. IL-4 rs2243250 and rs2227282 genotype frequencies in the latter were consistent with Hardy-Weinberg equilibrium (both P > 0.05). The TC+TT genotypes and T allele of rs2243250 were strongly associated with elevated AS risk [CC vs TC+TT: odds ratio (OR) = 2.378, 95% confidence interval (CI) = 1.746-3.239, P < 0.001; C vs T: OR = 2.588, 95%CI = 2.007-3.337, P < 0.001]. Moreover, the rs2227282 GG genotype and G allele may also correlate with increased risk (CC vs GC: OR = 1.555, 95%CI = 1.130-2.141, P = 0.007; CC vs GC+GG: OR = 1.833, 95%CI = 1.357-2.476, P < 0.001; C vs G: OR = 1.403, 95%CI = 1.086-1.811, P = 0.009). In addition, serum IL-4 concentrations were significantly lower in AS patients carrying the rs2243250 TT genotype compared to those with the CC and TC 2 X.L. Liu et al. Genetics and Molecular Research 15 (4): gmr15048898 genotypes (both P < 0.05). Similarly, patients carrying the rs2227282 CC genotype demonstrated higher serum IL-4 levels than those with the GC and GG genotypes (both P < 0.05). Our study provides evidence that IL-4 polymorphisms associated with diminished serum IL-4 levels may be partially responsible for AS development in the Chinese population.