There is increasing evidence supporting the relationship between bipolar disorder (BP) and neurotrophin. The present study investigated the relationship between neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene polymorphisms and bipolar I disorder (BP I) susceptibility and treatment response to mood stabilizers (lithium or valproate). Two-hundred eighty-four patients who met the DSM-IV criteria for BP I and 295 matched healthy controls were enrolled into this study. TaqMan® SNP genotyping assays were applied to genotype three NTRK2 gene polymorphisms (rs2769605, rs1565445, rs1387923). Our study showed a significant allelic association between NTRK2 gene polymorphism rs2769605 and treatment response to mood stabilizers in BP I patients (t = -2.53, P = 0.01). However, no significant association between NTRK2 gene polymorphisms and BP I susceptibility was observed after correcting for multiple comparisons. The results suggest that the NTRK2 gene polymorphism likely plays an essential role in treatment response to mood stabilizers in Han Chinese BP I patients.