Abstract: Paphia amabilis is an important fishery shellfish widely distributing along Southeast Asia coast. The muscles of its foot and siphons are commonly colored bright red-orange due to the presence of C37 skeletal carotenoids. However, 10.5%～18.6% of yellow-muscled individuals（YMs） were found among the four P. amabilis wild samples from Vietnam（CT, Co To island） and China（BH, BHA, Beihai, Guangxi Zhuang Autonomous Region; and ZJ, Zhanjiang, Guangdong Province）, the north of Beibu Gulf, South China Sea. Twenty genomic microsatellite markers were developed and 12 were employed to analyze the population genetic differentiation of three geographical populations（CT, BH, and ZJ, n=32/population）, as well as YM and RM（red-muscled） subpopulations. Medium levels of genetic diversity were detected in all three populations with the number of alleles ranging from 4～21（8.4±4.5） for CT, 4～16（7.6±3.3） for BH and 4～18（7.5±3.7） for ZJ. The average observed/expected heterozygosities were 0.66/0.66 for CT, 0.62/0.63 for BH, and 0.55/0.62 for ZJ, respectively. Total 4 out of 36 tests of microsatellites deviated from Hardy-Weinberg equilibrium（HWE, P＜0.05 after Bonferroni correction）, all in ZJ population due to the presence of null alleles suggested by MICRO-CHECKER. Exact test indicated highly significant differentiations(F_ST) between Vietnamese and two Chinese populations（0.099/0.123 between CT and BH/ZJ）. No allele of any microsatellite marker was found significantly associated with muscular coloration of P. amabilis, consequently no convergent microsatellite genetic differentiation presents between YM and RM subpopulations.