Background: The Yi people are considered the most primitive society in China, and live in the remote mountainous areas of Southwestern China. There have been no previous publications on genetic research concerning type 2 diabetes (T2D) in the Yi people. This is the first report that presents the association between SNP + 45 T > G (rs2241766) of the AdipoQ gene and T2D in Yi people. Our previous study showed that the prevalence of T2D in Yi people was lower than the national level in 2008. Genetic differences between Yi and Han people might be one possible explanation for this observation. Studies on the single nucleotide polymorphism SNP + 45 T > G (rs2241766) of the AdipoQ gene in Chinese Han people showed inconsistent results. This study was designed to identify genetic variants of the AdipoQ gene that contribute to the development of T2D in Yi and Han people. Methods: A case-control study on the association between SNP + 45 T > G (rs2241766) of the AdipoQ gene and T2D was carried out based on a cross-sectional study in the Liangshan area, Sichuan province in Southwestern China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to test for the presence of SNP + 45 T > G (rs2241766) in the AdipoQ gene. Results: Distributions of genotypes variants (TT/GG/TG) were not significantly different between T2D cases and controls both in Yi and Han people in China (p > 0.05). The allele frequencies (T/G) demonstrated a non-significant association with T2D, displaying OR of 1.1 (95 % CI: 0.8, 1.6) in Yi people and OR of 1.0 (95 % CI: 0.7, 1.4) in Han people. Conclusions: The SNP + 45 (rs2241766) of the AdipoQ gene is not associated with T2D neither in Yi nor in Han people in southwestern China.