Earlier this month, with a market capitalisation of about $346 billion, Apple briefly surpassed energy major Exxon Mobil to become the country's most valuable company.
The news of Jobs' resignation came after the markets closed on Wednesday.
In after-hours trading, Apple stock fell 5 per cent.
Jobs was diagnosed with a rare form of pancreatic cancer in 2004 and underwent a liver transplant two years ago.
In a letter in January this year, he said he was taking another leave of absence to 'focus on my health'.
He, however, emerged briefly from his medical leave during the year on a few occasions.
In March, he unveiled the second version of the revolutionary iPad and later attended a dinner hosted by President Barack Obama for technology tycoons in Silicon Valley.
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Steve Jobs poses with Apple's iBook portable computer at the MacWorld computer trade show.
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