The independence of the island doesn't endure. When Darios initially, and Xerxis later, abolishes the independence of the Ionian settlements and includes them in the Persian state, Kalymnos becomes part of that state, too. The island remains under the Persian dominion, which starts in the beginning of the 5th century B.C., until 478 B.C. However, from 477 or 476 B.C. the island seems to be part of the Athenian alliance along with Lesvos, Chios, Samos, Kos and Rhodes. Kalymnos is ruled by the Athenians until the abolishment of the Athenian sovereignty, but during this period it doesn't seem to participate in the Peloponesean War. Kalymnos becomes independent again and its state of government is the same as in the beginning of the Ancient Times.
When the Athenian alliance is formed again, Kalymnos is one of the islands which take part. It will remain in the alliance until 357. After the war between the allies though, ( 358 - 355 ) the island is no longer independent. Mafsolos, the king of Alikarnassos, becomes the ruler. After his death in 353, Kalymnos revolts but Queen Artemissia ( Mafsolos' widow ) subdues the island again in 352. Artemissia, and her successor Idreas, make the island part of the kingdom of Karia. However, after the death of Idreas, Kalymnos revolts, becomes independent once more and is united with the people of Athens.