In this study population genetic structure of Mnemiopsis leidyi were examined by 200 samples from the Caspian Sea. Samples were collected from Guilan province (Astara region), Mazandaran province (Amir Abad region), Golestan province (Gomishan region) and north part of the Caspian Sea. 50 samples were collected from each region. DNA was extracted by phenol - chlorophorm method and its concentration was 50 to 100 nanogram. PCR was performed using 18s rRNA gene. The PCR products of samples were digested by 12 restriction endonuclease enzymes. The digested products accompanied with standard marker (50 bp lader ). In order to measure fragment size samples were run on a 6% vertical polyacrylamide gel. The fragments were visualized by silver staining of the polyacrylamide gel. In this study, Dra I and Alu I enzymes showed different digestion pattern, as each of these enzymes had two genotypes. Other enzymes had similar digestion pattern. RAPD method used by 19 random primers. Ten of nineteen primers showed polymorphism patterns. Statistical analysis of data was performed by Popgene software. In this study, the maximum of genetic variation was in north of the Caspian Sea. Also, the maximum of genetic distance was between north area and Golestan coasts (0.089) and the minimum of genetic distance was between Mazandaran and Guilan coasts (0.001). The UOGMA dendogram showed two clusters. The samples of Mazandaran , Guilan and Golestan coasts placed in one cluster and samples of north area in other cluster The genetic diversity was significantly different between samples of north area and Golestan coasts (p≤0.05). As result, there is a significant genetic divergence between some of samples. Therefore, two genetic group of Mnemiopsis leidyi were identified in the Caspian Sea.