Since Saint Francis Xavier first introduced Christianity to Japan in 1549, there have been many religious conflicts in Japan. The first major conflict came about in 1587, when a ban was placed on Christianity that required all individuals belonging to the Christian faith to leave the country within 20 days of the ban. However, not many Christians left, as the ban was not strictly enforced.
Later, in 1614, Tokugawa Ieyasu issued another ban on Christianity. This ban, however, was very strictly enforced. Then, in 1622, the Tokugawa conducted the "Great Martyrdom", where 55 Christians were either decapitated or burned at the stake. It was not long after that, that all Spanish traders were expelled from Japan. Between the years of 1622, and 1637, nearly 6,000 Japanese Christians were executed for their faith.
Then, in 1637, a Christian daimyo rose up against the Tokugawa, and orchestrated the Shimabara Rebellion. Originally, though, the rebellion was not a matter of religion, but a rebellion against the Tokugawa's unfair taxation of Japanese citizens. It was not until later that the rebels declared their allegiance to God and Christian beliefs.
In 1638, nearly 37,000 rebels (farmers, women and children) took refuge in Shimabara castle, which was located near on the Shimabara Hanto. The Tokugawa pursued the rebels, and attacked the castle. It took the Tokugawa three months to penetrate the rebels' defenses, and they were only able to do so then because of the shortage of food and supplies that the rebels possessed. The Tokugawa slaughtered all but 105 of the rebels. However, this was not without a great loss, for almost 10,000 Tokugawa warriors were also killed in the three-month siege.
The result of this rebellion was ultimately the outlawing of all foreign contact with Japan, save for a small population of Dutch, who occupied Deshima Island, and occasional trade with the Chinese. This restriction on foreign contacts remained intact until the Meiji Period.
Also, thanks to liontamer and mauler for correcting typos and misinformation.