Officials have given no reason for Aghazadeh's resignation, which he reportedly handed in three weeks before it was announced on Thursday.
However, he has long been a close ally of Mir Hossein Mousavi, the reformist presidential candidate who demanded a re-run of recent elections which he claims were rigged.
Mahmoud Ahmadinejad, who was returned for a second term as president after the disputed election, has vowed to make "considerable changes" as he unveils a new government in the coming weeks.
On Thursday, he pledged that his new cabinet would be "10 times" more powerful than the previous one.
Open-minded administrator
Salehi is known as an open-minded administrator and was the person who signed a protocol with the IAEA in December 2003 which gave the UN agency a freer hand in inspecting Iran's nuclear sites.
But analysts questioned whether his appointment to the country's top nuclear job would bring any major changes to Iran's controversial nuclear policy as all decisions on the subject ultimately lie with Ayatollah Ali Khamenei, the supreme leader.
The West has called on Iran to halt the enrichment of uranium, which can be used to produce fuel for a nuclear reactor or a warhead for an atomic weapon.
Tehran, however, denies it wants to build an atomic bomb and insists that it has a right to develop a civilian nuclear programme to meet its energy needs.
Significant advances
Under Aghazadeh, the nuclear programme made several significant advances in the manufacture of centrifuges, a key component of the enrichment programme.
According to the IAEA, Iran has nearly 5,000 centrifuges currently enriching uranium for use as a nuclear fuel and another 2,000 others ready for operation.
Also on Thursday, Esfandiar Rahim Mashaie, currently the vice-president in charge of tourism, was announced as the new first vice-president, according to Iranian media.
Mashaie replaces Parviz Davoudi who is the current first vice-president. There are several other vice-presidents in Ahmadinejad's current line-up.