Abstract: Gastrodia elata (Orchidaceae) is a rare and endangered medicinal plant. Seven ISSR primers were used to examine population genetic parameters of 483 samples across eight natural populations and six cultivated populations of G. elata. The seven primers amplified a total of 77 unambiguous and reproducible bands, among which 64 bands were polymorphic and the percentage of polymorphic loci was PPB=83.12%. The results showed that genetic variation in the natural populations was significantly higher than that in the cultivated populations (PPB=59.09% vs. PPB=35.71%, Ae=1.29 vs. Ae=1.16, H=0.176 vs. H=0.100 and Shannon’s I=0.270 vs. I=0.155), suggesting that the cultivated populations are narrowly genetic-based and genetically uniform. UPGMA cluster analysis showed that natural populations and cultivated populations were distinctly separated into two groups. Coefficient of genetic differentiation among eight natural popula-tions was 0.2558 (G_ST) which was well in accordance with the result by AMOVA analysis (27.25% of the to-tal genetic variation resided among populations), indicating that natural populations were genetically differ-entiated to a certain extent. Gene flow among natural populations was relatively weak (N_m=1.4547), which might have caused the genetic differentiation among the populations. It is interesting to note that natural populations tended to cluster by geographical locations as revealed in UPGMA dendrogram, while the Mantel test showed no significant correlation between genetic and geographic distances among natural popula-tions(r=0.1669, P=0.2110). This incongruence suggested that the current genetic differentiation among natu-ral populations might have resulted from combined effects, including those of life history traits, geographical isolation and human disruption. The genetic uniformity found in cultivated populations might reflect the loss of genetic diversity caused by a genetic bottleneck during human domestication and clonal reproduction over generations. The narrow genetic base as revealed in cultivated G. elata and the genetic differentiation be-tween cultivated and natural populations might have resulted from a cutoff of gene exchange when domesti-cation began.