The Plateau Pika(Ochotona curzoniae) is endemic to the Qinghai-Tibetan Plateau and is a key species in the alpine meadow ecosystem.In this paper,genetic diversity and differentiation of four populations of Plateau Pika from both banks of the Brahmaputra River were assessed with inter-simple sequence repeat(ISSR) and Cyt b gene sequences.Our results showed that the genetic diversity of Plateau Pika was relatively high and there were much larger deviations among populations based on Cyt b gene than those based on ISSR marker.Analysis of molecular variance(AMOVA) in ISSR revealed a low level of genetic differentiation among the four populations.Of the total genetic variance,13.50% was attributable to among-population variance,and the results of the UPGMA cluster analysis indicated that populations from north bank and south bank of the Brahmaputra River were intersectant.However,AMOVA in Cyt b gene indicated that 79.24% of the total genetic variance was explained by differences among the four populations,and the UPGMA cluster of the four populations demonstrated that the populations from north bank and south bank were clustered into two single groups,respectively.Therefore,we suggest that Cyt b gene is a better marker than ISSR in reflecting the genetic diversity and genetic differentiation of populations.