The Roman Emperor Julian is killed invading the Persian empire in 363 AD, one of several wars between the two empires over the control of Armenia and Syria. A treaty partitioning Armenia helped ease tensions, but more important were nomad attacks on the eastern frontier of the Persian empire after 440 AD. These were a branch of the Mongols, called the White Huns. The Persian shah is killed fighting the White Huns in 484, but the empire survives.

Shah Khosru Parviz (590-628 AD) led the last great expansion of the Persian empire. Between 607-615, Armenia was re-occupied while all the Roman fortresses in Mesopotamia were captured. In 616, Khosru took Roman Egypt, and the Eastern Roman Empire was facing total defeat. Constantinople itself was besieged, but the Roman Emperor Heraclius allied with the Khazars and held off the Persians for ten years. Then in 626, the Romans counter-attacked and reached the Persian capital. Khosru was murdered by his nobles and peace was made in 628.

Two major trade routes passed through Persia. Control of these routes was one of the main points of rivalry between the Persians and the Romans. One was the famous overland Silk Route which reached from China and Japan in the east to Rome in the west. The other was the Spice Route, which began in southeast Asia and India, crossed the Indian Ocean and Persian Gulf, then went up the Euphrates and Tigris rivers, and finally joined the Silk Route in Persian Mesopotamia (the modern state of Iraq). As might be expected, the main product carried on the Silk Route was silk cloth from China and central Asia.

Making silk threads from the cocoons spun by the silk-worm caterpillar originated in China. How and by whom we do not know, but a spy or spies eventually got the secret out. By 550 AD, the secret of silk making had reached Rome. The "spice" trade not only included spices such as pepper, cloves and cinnamon, but also dyes, perfumes and incense, medicines and gum. Gum, a thick kind of tree sap, in ancient and medieval times was used for glue and for many things for which we now use synthetic rubber and plastic.