During the widespread rebellion against Wang Mang, the Korean state of Goguryeo was free to raid Han's Korean commanderies; Han did not reaffirm its control over the region until 30 CE. The Trưng Sisters of Vietnam rebelled against Han in 40 CE. Their rebellion was crushed by Han general Ma Yuan (d. 49 CE) in a campaign from 42–43 CE. Wang Mang renewed hostilities against the Xiongnu, who were estranged from Han until their leader Bi (比), a rival claimant to the throne against his cousin Punu (蒲奴), submitted to Han as a tributary vassal in 50 CE. This created two rival Xiongnu states: the Southern Xiongnu led by Bi, an ally of Han, and the Northern Xiongnu led by Punu, an enemy of Han.
During the turbulent reign of Wang Mang, Han lost control over the Tarim Basin, which was conquered by the Northern Xiongnu in 63 CE and used as a base to invade Han's Hexi Corridor in Gansu. Dou Gu (d. 88 CE) defeated the Northern Xiongnu at the Battle of Yiwulu in 73 CE, evicting them from Turpan and chasing them as far as Lake Barkol before establishing a garrison at Hami. After the new Protector General of the Western Regions Chen Mu (d. 75 CE) was killed by allies of the Xiongnu in Karasahr and Kucha, the garrison at Hami was withdrawn. At the Battle of Ikh Bayan in 89 CE, Dou Xian (d. 92 CE) defeated the Northern Xiongnu chanyu who then retreated into the Altai Mountains. After the Northern Xiongnu fled into the Ili River valley in 91 CE, the nomadic Xianbei occupied the area from the borders of the Buyeo Kingdom in Manchuria to the Ili River of the Wusun people. The Xianbei reached their apogee under Tanshihuai (檀石槐) (d. 180 CE), who consistently defeated Chinese armies. However, Tanshihuai's confederation disintegrated after his death.
Ban Chao (d. 102 CE) enlisted the aid of the Kushan Empire, occupying the area of modern India, Pakistan, Afghanistan, and Tajikistan, to subdue Kashgar and its ally Sogdiana. When a request by Kushan ruler Vima Kadphises (r. c. 90–c. 100 CE) for a marriage alliance with the Han was rejected in 90 CE, he sent his forces to Wakhan (Afghanistan) to attack Ban Chao. The conflict ended with the Kushans withdrawing because of lack of supplies. In 91 CE, the office of Protector General of the Western Regions was reinstated when it was bestowed on Ban Chao.
In addition to tributary relations with the Kushans, the Han Empire received gifts from the Parthian Empire, from a king in modern Burma, from a ruler in Japan, and initiated an unsuccessful mission to Daqin (Rome) in 97 CE with Gan Ying as emissary. A Roman embassy of Emperor Marcus Aurelius (r. 161–180 CE) is believed to have reached the court of Emperor Huan of Han (r. 146–168 CE) in 166 CE, yet Rafe de Crespigny asserts that this was most likely a group of Roman merchants. Other travelers to Eastern-Han China included Buddhist monks who translated works into Chinese, such as An Shigao of Parthia, and Lokaksema from Kushan-era Gandhara, India.
