The economic prosperity of Rhodes was suspended during the Greco-Persian wars, in which the island, sharing the fate of other Greek cities of Asia Minor, was forced to side with the Persians. During the Peloponnesian War, Rhodes, As a member of the Athens Sea Union, took the side of Athens, to 412 BC, the island and then moved to the side of Sparta. In 408 BC, at the initiative of the oligarchic parties, the three cities of the island decided to unite and establish a new a town called Rhodes, which was built on the northern edge of the island. New city plan was drawn up by Gippodamovoy system, with smooth and wide streets, which intersect each other at right angles. Centre City had a large agora (marketplace). City favorably with its technically advanced sewer system, strong walls and five ports.

The symbol of the new city became the image of the sun god Helios and the nymph of Rhodes, as well as a rose. In the early years of the 4th century BC Rhodes was in the sphere of influence is that of Sparta, Athens, until the mid-century tyrant of Caria Mausolos not set in Rhodes Gegesiloha power. After the death of Mausolos power inherited by his wife Artemisia, who through cunning managed to capture Rhodes. In 343 BC the island's inhabitants expelled the Carian garrison, and later made on the side of Alexander of Macedon. During the wars between the Diadochi (Heirs of Alexander), Rhodes tried to remain neutral, but long to stay on the sidelines and could not in 305 BC was besieged by troops of Demetrius. Known as Poliorket (osazhdatel) Demetrius has used the most modern siege machines, but have not been able to capture the city due to its strong walls and valor of the inhabitants of the city. In memory of his great victory residents of Rhodes erected one of the wonders of the Ancient World – Colossus of Rhodes.