During the sixteenth century, traders and Jesuit missionaries from Portugal reached Japan for the first time, initiating active commercial and cultural exchange between Japan and the West (Nanban trade).

Oda Nobunaga conquered numerous other daimyo by using European technology and firearms and had almost unified the nation when he was assassinated in 1582. Toyotomi Hideyoshi succeeded Nobunaga and united the nation in 1590. Hideyoshi invaded Korea twice, but following several defeats by Korean and Ming China forces and Hideyoshi's death, Japanese troops were withdrawn in 1598.

After Hideyoshi's death, Tokugawa Ieyasu utilized his position as regent for Hideyoshi's son Toyotomi Hideyori to gain political and military support. When open war broke out, he defeated rival clans in the Battle of Sekigahara in 1600. Ieyasu was appointed sh?gun in 1603 and established the Tokugawa shogunate at Edo (modern Tokyo). The Tokugawa shogunate enacted a variety of measures such as Buke shohatto to control the autonomous daimyo. In 1639, the shogunate began the isolationist sakoku ("closed country") policy that spanned the two and a half centuries of tenuous political unity known as the Edo period. The study of Western sciences, known as rangaku, continued during this period through contacts with the Dutch enclave at Dejima in Nagasaki. The Edo period also gave rise to kokugaku, or literally "national studies", the study of Japan by the Japanese themselves.

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