Multan District was agricultural region with forests during the Indus Valley Civilization. The Vedic period is characterized by Indo-Aryan culture that invaded from Central Asia and settled in Punjab region. The Kambojas, Daradas, Kaikayas, Madras, Pauravas, Yaudheyas, Malavas and Kurus invaded, settled and ruled ancient Punjab region. After overrunning the Achaemenid Empire in 331 BCE, Alexander marched into present-day Punjab region with an army of 50,000. The Multan was ruled by Maurya Empire, Indo-Greek kingdom, Kushan Empire, Gupta Empire, White Huns, Kushano-Hephthalites and Shahi kingdoms.
In 712 A.D. Muhammad Bin Qasim conquered the Multan, made Muslim governance and the region became the part of Umayyad caliphate. After Muhammad Bin Qasim, in 997 CE, Sultan Mahmud Ghaznavi, took over the Ghaznavid dynasty empire established by his father, Sultan Sebuktegin, In 1005 he conquered the Shahis in Kabul in 1005, and followed it by the conquests of Punjab region. The Delhi Sultanate and later Mughal Empire ruled the region. The Punjab region became predominantly Muslim due to missionary Sufi saints whose dargahs dot the landscape of Punjab region.
After the decline of the Mughal Empire, the Sikh Empire invaded and occupied Multan District. The Muslims faced restrictions during the Sikh rule. During the period of British rule, Multan district increased in population and importance.
The predominantly Muslim population supported Muslim League and Pakistan Movement. After the independence of Pakistan in 1947, the minority Hindus and Sikhs migrated to India while the Muslim refugees from India settled in the Multan District.
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